Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2008 (2008), Article ID 769413, 19 pages
http://dx.doi.org/10.1155/2008/769413
Review Article

CXCR4 in Cancer and Its Regulation by PPARγ

1Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5
2Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1

Received 4 April 2008; Revised 25 June 2008; Accepted 10 July 2008

Academic Editor: Dipak Panigrahy

Copyright © 2008 Cynthia Lee Richard and Jonathan Blay. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Balabanian, B. Lagane, S. Infantino et al., “The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes,” The Journal of Biological Chemistry, vol. 280, no. 42, pp. 35760–35766, 2005. View at Publisher · View at Google Scholar
  2. P. M. Murphy, M. Baggiolini, I. F. Charo et al., “International union of pharmacology. XXII. Nomenclature for chemokine receptors,” Pharmacological Reviews, vol. 52, no. 1, pp. 145–176, 2000. View at Google Scholar
  3. M. Mellado, J. M. Rodríguez-Frade, S. Mañes, and C. Martínez-A, “Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation,” Annual Review of Immunology, vol. 19, pp. 397–421, 2001. View at Publisher · View at Google Scholar
  4. D. Rossi and A. Zlotnik, “The biology of chemokines and their receptors,” Annual Review of Immunology, vol. 18, pp. 217–243, 2000. View at Publisher · View at Google Scholar
  5. S. M. Foord, T. I. Bonner, R. R. Neubig et al., “International Union of Pharmacology. XLVI. G protein-coupled receptor list,” Pharmacological Reviews, vol. 57, no. 2, pp. 279–288, 2005. View at Publisher · View at Google Scholar
  6. M. Loetscher, T. Geiser, T. O'Reilly, R. Zwahlen, M. Baggiolini, and B. Moser, “Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes,” The Journal of Biological Chemistry, vol. 269, no. 1, pp. 232–237, 1994. View at Google Scholar
  7. Y. Feng, C. C. Broder, P. E. Kennedy, and E. A. Berger, “HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor,” Science, vol. 272, no. 5263, pp. 872–877, 1996. View at Publisher · View at Google Scholar
  8. C. C. Bleul, M. Farzan, H. Choe et al., “The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry,” Nature, vol. 382, no. 6594, pp. 829–833, 1996. View at Publisher · View at Google Scholar
  9. E. Oberlin, A. Amara, F. Bachelerie et al., “The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1,” Nature, vol. 382, no. 6594, pp. 833–835, 1996. View at Publisher · View at Google Scholar
  10. A. Caruz, M. Samsom, J. M. Alonso et al., “Genomic organization and promoter characterization of human CXCR4 gene,” FEBS Letters, vol. 426, no. 2, pp. 271–278, 1998. View at Publisher · View at Google Scholar
  11. S. A. Wegner, P. K. Ehrenberg, G. Chang, D. E. Dayhoff, A. L. Sleeker, and N. L. Michael, “Genomic organization and functional characterization of the chemokine receptor CXCR4, a major entry co-receptor for human immunodeficiency virus type 1,” The Journal of Biological Chemistry, vol. 273, no. 8, pp. 4754–4760, 1998. View at Publisher · View at Google Scholar
  12. L. Zhang, T. He, A. Talal, G. Wang, S. S. Frankel, and D. D. Ho, “In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, AND CCR5,” Journal of Virology, vol. 72, no. 6, pp. 5035–5045, 1998. View at Google Scholar
  13. F. Balkwill, “The significance of cancer cell expression of the chemokine receptor CXCR4,” Seminars in Cancer Biology, vol. 14, no. 3, pp. 171–179, 2004. View at Publisher · View at Google Scholar
  14. M. Shirozu, T. Nakano, J. Inazawa et al., “Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene,” Genomics, vol. 28, no. 3, pp. 495–500, 1995. View at Publisher · View at Google Scholar
  15. T. Nagasawa, S. Hirota, K. Tachibana et al., “Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1,” Nature, vol. 382, no. 6592, pp. 635–638, 1996. View at Publisher · View at Google Scholar
  16. K. Tachibana, S. Hirota, H. Iizasa et al., “The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract,” Nature, vol. 393, no. 6685, pp. 591–594, 1998. View at Publisher · View at Google Scholar
  17. Y. R. Zou, A. H. Kottmann, M. Kuroda, I. Taniuchi, and D. R. Littman, “Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development,” Nature, vol. 393, no. 6685, pp. 595–599, 1998. View at Publisher · View at Google Scholar
  18. A. Aiuti, I. J. Webb, C. Bleul, T. Springer, and J.C. Gutierrez-Ramos, “The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood,” Journal of Experimental Medicine, vol. 185, no. 1, pp. 111–120, 1997. View at Publisher · View at Google Scholar
  19. P. A. Hernandez, R. J. Gorlin, J. N. Lukens et al., “Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease,” Nature Genetics, vol. 34, no. 1, pp. 70–74, 2003. View at Publisher · View at Google Scholar
  20. M. Kucia, R. Reca, K. Miekus et al., “Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis,” Stem Cells, vol. 23, no. 7, pp. 879–894, 2005. View at Publisher · View at Google Scholar
  21. J. Imitola, K. Raddassi, K. I. Park et al., “Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 52, pp. 18117–18122, 2004. View at Publisher · View at Google Scholar
  22. C. Gao and Y. Li, “SDF-1 plays a key role in the repairing and remodeling process on rat allo-orthotopic abdominal aorta grafts,” Transplantation Proceedings, vol. 39, no. 1, pp. 268–272, 2007. View at Publisher · View at Google Scholar
  23. H. Kajiyama, K. Shibata, K. Ino, A. Nawa, S. Mizutani, and F. Kikkawa, “Possible involvement of SDF-1α/CXCR4-DPPIV axis in TGF-β1-induced enhancement of migratory potential in human peritoneal mesothelial cells,” Cell & Tissue Research, vol. 330, no. 2, pp. 221–229, 2007. View at Publisher · View at Google Scholar
  24. R. A. Moyer, M. K. Wendt, P. A. Johanesen, J. R. Turner, and M. B. Dwinell, “Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia,” Laboratory Investigation, vol. 87, no. 8, pp. 807–817, 2007. View at Publisher · View at Google Scholar
  25. A. Müller, B. Homey, H. Soto et al., “Involvement of chemokine receptors in breast cancer metastasis,” Nature, vol. 410, no. 6824, pp. 50–56, 2001. View at Publisher · View at Google Scholar
  26. C. J. Scotton, J. L. Wilson, D. Milliken, G. Stamp, and F. R. Balkwill, “Epithelial cancer cell migration: a role for chemokine receptors?” Cancer Research, vol. 61, no. 13, pp. 4961–4965, 2001. View at Google Scholar
  27. K.-I. Oonakahara, W. Matsuyama, I. Higashimoto, M. Kawabata, K. Arimura, and M. Osame, “Stromal-derived factor-1α/CXCL12-CXCR 4 axis is involved in the dissemination of NSCLC cells into pleural space,” American Journal of Respiratory Cell and Molecular Biology, vol. 30, no. 5, pp. 671–677, 2004. View at Publisher · View at Google Scholar
  28. M. Kato, J. Kitayama, S. Kazama, and H. Nagawa, “Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma,” Breast Cancer Research, vol. 5, no. 5, pp. R144–R150, 2003. View at Publisher · View at Google Scholar
  29. R. S. Taichman, C. Cooper, E. T. Keller, K. J. Pienta, N. S. Taichman, and L. K. McCauley, “Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone,” Cancer Research, vol. 62, no. 6, pp. 1832–1837, 2002. View at Google Scholar
  30. C. H. Tang, J. Y. Chuang, Y. C. Fong, M. C. Maa, T. D. Way, and C. H. Hung, “Bone-derived SDF-1 stimulates IL-6 Release via CXCR4, ERK and NF-κB pathways and promoting osteoclastogenesis in human oral cancer cells,” Carcinogenesis. In press. View at Publisher · View at Google Scholar
  31. C. L. Richard, E. Y. Tan, and J. Blay, “Adenosine upregulates CXCR4 and enhances the proliferative and migratory responses of human carcinoma cells to CXCL12/SDF-1α,” International Journal of Cancer, vol. 119, no. 9, pp. 2044–2053, 2006. View at Publisher · View at Google Scholar
  32. Y.-X. Sun, J. Wang, C. E. Shelburne et al., “Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo,” Journal of Cellular Biochemistry, vol. 89, no. 3, pp. 462–473, 2003. View at Publisher · View at Google Scholar
  33. C. J. Scotton, J. L. Wilson, K. Scott et al., “Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer,” Cancer Research, vol. 62, no. 20, pp. 5930–5938, 2002. View at Google Scholar
  34. I. Kryczek, A. Lange, P. Mottram et al., “CXCL12 and vascular endothelial growth factor synergistically induce neonaniogenisis in human ovarian cancers,” Cancer Research, vol. 65, no. 2, pp. 465–472, 2005. View at Google Scholar
  35. R. A. Bartolomé, B. G. Gálvez, N. Longo et al., “Stromal cell-derived factor-1α promotes melanoma cell invasion across basement membranes involving stimulation of membrane-type 1 matrix metalloproteinase and Rho GTPase activities,” Cancer Research, vol. 64, no. 7, pp. 2534–2543, 2004. View at Publisher · View at Google Scholar
  36. S. Singh, U. P. Singh, W. E. Grizzle, and J. W. Lillard Jr., “CXCL12-CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion,” Laboratory Investigation, vol. 84, no. 12, pp. 1666–1676, 2004. View at Publisher · View at Google Scholar
  37. J. Libura, J. Drukala, M. Majka et al., “CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis, and adhesion,” Blood, vol. 100, no. 7, pp. 2597–2606, 2002. View at Publisher · View at Google Scholar
  38. L. Hao, C. Zhang, Y. Qiu et al., “Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer,” Cancer Letters, vol. 253, no. 1, pp. 34–42, 2007. View at Publisher · View at Google Scholar
  39. J.-K. Li, L. Yu, Y. Shen, L.-S. Zhou, Y.-C. Wang, and J.-H. Zhang, “Inhibition of CXCR4 activity with AMD3100 decreases invasion of human colorectal cancer cells in vitro,” World Journal of Gastroenterology, vol. 14, no. 15, pp. 2308–2313, 2008. View at Publisher · View at Google Scholar
  40. A. Ottaiano, A. di Palma, M. Napolitano et al., “Inhibitory effects of anti-CXCR4 antibodies on human colon cancer cells,” Cancer Immunology, Immunotherapy, vol. 54, no. 8, pp. 781–791, 2005. View at Publisher · View at Google Scholar
  41. H. Geminder, O. Sagi-Assif, L. Goldberg et al., “A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma,” The Journal of Immunology, vol. 167, no. 8, pp. 4747–4757, 2001. View at Google Scholar
  42. F. Marchesi, P. Monti, B. E. Leone et al., “Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4,” Cancer Research, vol. 64, no. 22, pp. 8420–8427, 2004. View at Publisher · View at Google Scholar
  43. A. R. Cardones, T. Murakami, and S. T. Hwang, “CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via β1 integrin,” Cancer Research, vol. 63, no. 20, pp. 6751–6757, 2003. View at Google Scholar
  44. T. N. Hartmann, J. A. Burger, A. Glodek, N. Fujii, and M. Burger, “CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells,” Oncogene, vol. 24, no. 27, pp. 4462–4471, 2005. View at Publisher · View at Google Scholar
  45. B.-C. Lee, T.-H. Lee, S. Avraham, and H. K. Avraham, “Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1α in breast cancer cell migration through human brain microvascular endothelial cells,” Molecular Cancer Research, vol. 2, no. 6, pp. 327–338, 2004. View at Google Scholar
  46. O. Salvucci, A. Bouchard, A. Baccarelli et al., “The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study,” Breast Cancer Research and Treatment, vol. 97, no. 3, pp. 275–283, 2006. View at Publisher · View at Google Scholar
  47. B. C. Schmid, M. Rudas, G. A. Rezniczek, S. Leodolter, and R. Zeillinger, “CXCR4 is expressed in ductal carcinoma in situ of the breast and in atypical ductal hyperplasia,” Breast Cancer Research and Treatment, vol. 84, no. 3, pp. 247–250, 2004. View at Publisher · View at Google Scholar
  48. A. Zlotnik, “Chemokines and cancer,” International Journal of Cancer, vol. 119, no. 9, pp. 2026–2029, 2006. View at Publisher · View at Google Scholar
  49. M. C. P. Smith, K. E. Luker, J. R. Garbow et al., “CXCR4 regulates growth of both primary and metastatic breast cancer,” Cancer Research, vol. 64, no. 23, pp. 8604–8612, 2004. View at Publisher · View at Google Scholar
  50. N. Cabioglu, Y. Gong, R. Islam et al., “Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer,” Annals of Oncology, vol. 18, no. 6, pp. 1021–1029, 2007. View at Publisher · View at Google Scholar
  51. Y.-C. Su, M.-T. Wu, C.-J. Huang, M.-F. Hou, S.-F. Yang, and C.-Y. Chai, “Expression of CXCR4 is associated with axillary lymph node status in patients with early breast cancer,” The Breast, vol. 15, no. 4, pp. 533–539, 2006. View at Publisher · View at Google Scholar
  52. H. Kang, G. Watkins, A. Douglas-Jones, R. E. Mansel, and W. G. Jiang, “The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer,” The Breast, vol. 14, no. 5, pp. 360–367, 2005. View at Publisher · View at Google Scholar
  53. S. U. Woo, J. W. Bae, C. H. Kim, J. B. Lee, and B. W. Koo, “A significant correlation between nuclear CXCR4 expression and axillary lymph node metastasis in hormonal receptor negative breast cancer,” Annals of Surgical Oncology, vol. 15, no. 1, pp. 281–285, 2008. View at Publisher · View at Google Scholar
  54. L. A. Kingsley, P. G. J. Fournier, J. M. Chirgwin, and T. A. Guise, “Molecular biology of bone metastasis,” Molecular Cancer Therapeutics, vol. 6, no. 10, pp. 2609–2617, 2007. View at Publisher · View at Google Scholar
  55. X. Cheng and M.-C. Hung, “Breast cancer brain metastases,” Cancer and Metastasis Reviews, vol. 26, no. 3-4, pp. 635–643, 2007. View at Publisher · View at Google Scholar
  56. N. Cabioglu, M. S. Yazici, B. Arun et al., “CCR7 and CXCR4 as novel biomarkers predicting axillary lymph node metastasis in T1 breast cancer,” Clinical Cancer Research, vol. 11, no. 16, pp. 5686–5693, 2005. View at Publisher · View at Google Scholar
  57. V. N. Dupont, D. Gentien, M. Oberkampf, Y. De Rycke, and N. Blin, “A gene expression signature associated with metastatic cells in effusions of breast carcinoma patients,” International Journal of Cancer, vol. 121, no. 5, pp. 1036–1046, 2007. View at Publisher · View at Google Scholar
  58. R. Crazzolara, A. Kreczy, G. Mann et al., “High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia,” British Journal of Haematology, vol. 115, no. 3, pp. 545–553, 2001. View at Publisher · View at Google Scholar
  59. A. C. Spoo, M. Lübbert, W. G. Wierda, and J. A. Burger, “CXCR4 is a prognostic marker in acute myelogenous leukemia,” Blood, vol. 109, no. 2, pp. 786–791, 2007. View at Publisher · View at Google Scholar
  60. A. Sehgal, C. Keener, A. L. Boynton, J. Warrick, and G. P. Murphy, “CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells,” Journal of Surgical Oncology, vol. 69, no. 2, pp. 99–104, 1998. View at Publisher · View at Google Scholar
  61. S. Barbero, A. Bajetto, R. Bonavia et al., “Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro,” Annals of the New York Academy of Sciences, vol. 973, pp. 60–69, 2002. View at Google Scholar
  62. Y. Zhou, P. H. Larsen, C. Hao, and V. W. Yong, “CXCR4 is a major chemokine receptor on glioma cells and mediates their survival,” The Journal of Biological Chemistry, vol. 277, no. 51, pp. 49481–49487, 2002. View at Publisher · View at Google Scholar
  63. J. B. Rubin, A. L. Kung, R. S. Klein et al., “A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 23, pp. 13513–13518, 2003. View at Publisher · View at Google Scholar
  64. X.-W. Bian, S.-X. Yang, J.-H. Chen et al., “Preferential expression of chemokine receptor CXCR4 by highly malignant human gliomas and its association with poor patient survival,” Neurosurgery, vol. 61, no. 3, pp. 570–579, 2007. View at Google Scholar
  65. N. Cabioglu, J. Summy, C. Miller et al., “CXCL-12/stromal cell-derived factor-1α transactivates HER2-neu in breast cancer cells by a novel pathway involving Src kinase activation,” Cancer Research, vol. 65, no. 15, pp. 6493–6497, 2005. View at Publisher · View at Google Scholar
  66. F. Andre, N. Cabioglu, H. Assi et al., “Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer,” Annals of Oncology, vol. 17, no. 6, pp. 945–951, 2006. View at Publisher · View at Google Scholar
  67. H. Shim, S. K. Lau, S. Devi, Y. Yoon, H. T. Cho, and Z. Liang, “Lower expression of CXCR4 in lymph node metastases than in primary breast cancers: potential regulation by ligand-dependent degradation and HIF-1α,” Biochemical and Biophysical Research Communications, vol. 346, no. 1, pp. 252–258, 2006. View at Publisher · View at Google Scholar
  68. J. Kodama, Hasengaowa, T. Kusumoto et al., “Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer,” Annals of Oncology, vol. 18, no. 1, pp. 70–76, 2007. View at Publisher · View at Google Scholar
  69. R. Möhle, C. Failenschmid, F. Bautz, and L. Kanz, “Overexpression of the chemokine receptor CXCR4 in B cell chronic lymphocytic leukemia is associated with increased functional response to stromal cell-derived factor-1 (SDF-1),” Leukemia, vol. 13, no. 12, pp. 1954–1959, 1999. View at Publisher · View at Google Scholar
  70. N. Ishibe, M. Albitar, I. B. Jilani, L. R. Goldin, G. E. Marti, and N. E. Caporaso, “CXCR4 expression is associated with survival in familial chronic lymphocytic leukemia, but CD38 expression is not,” Blood, vol. 100, no. 3, pp. 1100–1101, 2002. View at Publisher · View at Google Scholar
  71. I. S. Zeelenberg, L. Ruuls-Van Stalle, and E. Roos, “The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases,” Cancer Research, vol. 63, no. 13, pp. 3833–3839, 2003. View at Google Scholar
  72. C. C. Schimanski, S. Schwald, N. Simiantonaki et al., “Effect of chemokine receptors CXCR4 and CCR7 on the metastatic behavior of human colorectal cancer,” Clinical Cancer Research, vol. 11, no. 5, pp. 1743–1750, 2005. View at Publisher · View at Google Scholar
  73. J. Kim, H. Takeuchi, S. T. Lam et al., “Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival,” Journal of Clinical Oncology, vol. 23, no. 12, pp. 2744–2753, 2005. View at Publisher · View at Google Scholar
  74. S. Fukunaga, K. Maeda, E. Noda, T. Inoue, K. Wada, and K. Hirakawa, “Association between expression of vascular endothelial growth factor C, chemokine receptor CXCR4 and lymph node metastasis in colorectal cancer,” Oncology, vol. 71, no. 3-4, pp. 204–211, 2006. View at Publisher · View at Google Scholar
  75. A. Ottaiano, R. Franco, A. A. Talamanca et al., “Overexpression of both CXC chemokine receptor 4 and vascular endothelial growth factor proteins predicts early distant relapse in stage II-III colorectal cancer patients,” Clinical Cancer Research, vol. 12, no. 9, pp. 2795–2803, 2006. View at Publisher · View at Google Scholar
  76. Y. Mizokami, H. Kajiyama, K. Shibata, K. Ino, F. Kikkawa, and S. Mizutani, “Stromal cell-derived factor-1α-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma,” International Journal of Cancer, vol. 110, no. 5, pp. 652–659, 2004. View at Publisher · View at Google Scholar
  77. J. T. Kaifi, E. F. Yekebas, P. Schurr et al., “Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer,” Journal of the National Cancer Institute, vol. 97, no. 24, pp. 1840–1847, 2005. View at Publisher · View at Google Scholar
  78. K. Yasumoto, K. Koizumi, A. Kawashima et al., “Role of the CXCL12/CXCR4 axis in peritoneal carcinomatosis of gastric cancer,” Cancer Research, vol. 66, no. 4, pp. 2181–2187, 2006. View at Publisher · View at Google Scholar
  79. A. Katayama, T. Ogino, N. Bandoh, S. Nonaka, and Y. Harabuchi, “Expression of CXCR4 and its down-regulation by IFN-γ in head and neck squamous cell carcinoma,” Clinical Cancer Research, vol. 11, no. 8, pp. 2937–2946, 2005. View at Publisher · View at Google Scholar
  80. M. Taki, K. Higashikawa, S. Yoneda et al., “Up-regulation of stromal cell-derived factor-1α and its receptor CXCR4 expression accompanied with epithelial-mesenchymal transition in human oral squamous cell carcinoma,” Oncology Reports, vol. 19, no. 4, pp. 993–998, 2008. View at Google Scholar
  81. C. C. Schimanski, R. Bahre, I. Gockel et al., “Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4,” British Journal of Cancer, vol. 95, no. 2, pp. 210–217, 2006. View at Publisher · View at Google Scholar
  82. M. M. Robledo, R. A. Bartolomé, N. Longo et al., “Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma cells,” The Journal of Biological Chemistry, vol. 276, no. 48, pp. 45098–45105, 2001. View at Publisher · View at Google Scholar
  83. S. Scala, A. Ottaiano, P. A. Ascierto et al., “Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma,” Clinical Cancer Research, vol. 11, no. 5, pp. 1835–1841, 2005. View at Publisher · View at Google Scholar
  84. F. Sanz-Rodríguez, A. Hidalgo, and J. Teixidó, “Chemokine stromal cell-derived factor-1α modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1,” Blood, vol. 97, no. 2, pp. 346–351, 2001. View at Publisher · View at Google Scholar
  85. J. Hu, X. Deng, X. Bian et al., “The expression of functional chemokine receptor CXCR4 is associated with the metastatic potential of human nasopharyngeal carcinoma,” Clinical Cancer Research, vol. 11, no. 13, pp. 4658–4665, 2005. View at Publisher · View at Google Scholar
  86. F. Bertolini, C. Dell'Agnola, P. Mancuso et al., “CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin's lymphoma,” Cancer Research, vol. 62, no. 11, pp. 3106–3112, 2002. View at Google Scholar
  87. J. Basile, B. Thiers, J. Maize Sr., and D. M. R. Lathers, “Chemokine receptor expression in non-melanoma skin cancer,” Journal of Cutaneous Pathology, vol. 35, no. 7, pp. 623–629, 2008. View at Publisher · View at Google Scholar
  88. L. Su, J. Zhang, H. Xu et al., “Differential expression of CXCR4 is associated with the metastatic potential of human non-small cell lung cancer cells,” Clinical Cancer Research, vol. 11, no. 23, pp. 8273–8280, 2005. View at Publisher · View at Google Scholar
  89. J.-P. Spano, F. Andre, L. Morat et al., “Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome,” Annals of Oncology, vol. 15, no. 4, pp. 613–617, 2004. View at Publisher · View at Google Scholar
  90. C. Laverdiere, B. H. Hoang, R. Yang et al., “Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma,” Clinical Cancer Research, vol. 11, no. 7, pp. 2561–2567, 2005. View at Publisher · View at Google Scholar
  91. Y. Oda, H. Yamamoto, S. Tamiya et al., “CXCR4 and VEGF expression in the primary site and the metastatic site of human osteosarcoma: analysis within a group of patients, all of whom developed lung metastasis,” Modern Pathology, vol. 19, no. 5, pp. 738–745, 2006. View at Publisher · View at Google Scholar
  92. Y.-p. Jiang, X.-H. Wu, B. Shi, W.-X. Wu, and G.-R. Yin, “Expression of chemokine CXCL12 and its receptor CXCR4 in human epithelial ovarian cancer: an independent prognostic factor for tumor progression,” Gynecologic Oncology, vol. 103, no. 1, pp. 226–233, 2006. View at Publisher · View at Google Scholar
  93. T. Koshiba, R. Hosotani, Y. Miyamoto et al., “Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: a possible role for tumor progression,” Clinical Cancer Research, vol. 6, no. 9, pp. 3530–3535, 2000. View at Google Scholar
  94. H. Mochizuki, A. Matsubara, J. Teishima et al., “Interaction of ligand-receptor system between stromal-cell-derived factor-1 and CXC chemokine receptor 4 in human prostate cancer: a possible predictor of metastasis,” Biochemical and Biophysical Research Communications, vol. 320, no. 3, pp. 656–663, 2004. View at Publisher · View at Google Scholar
  95. T. Akashi, K. Koizumi, K. Tsuneyama, I. Saiki, Y. Takano, and H. Fuse, “Chemokine receptor CXCR4 expression and prognosis in patients with metastatic prostate cancer,” Cancer Science, vol. 99, no. 3, pp. 539–542, 2008. View at Publisher · View at Google Scholar
  96. A. J. Schrader, O. Lechner, M. Templin et al., “CXCR4/CXCL12 expression and signalling in kidney cancer,” British Journal of Cancer, vol. 86, no. 8, pp. 1250–1256, 2002. View at Publisher · View at Google Scholar
  97. P. Staller, J. Sulitkova, J. Lisztwan, H. Moch, E. J. Oakeley, and W. Krek, “Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL,” Nature, vol. 425, no. 6955, pp. 307–311, 2003. View at Publisher · View at Google Scholar
  98. T. Kijima, G. Maulik, P. C. Ma et al., “Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells,” Cancer Research, vol. 62, no. 21, pp. 6304–6311, 2002. View at Google Scholar
  99. J. H. Hwang, J. H. Hwang, H. K. Chung et al., “CXC chemokine receptor 4 expression and function in human anaplastic thyroid cancer cells,” The Journal of Clinical Endocrinology & Metabolism, vol. 88, no. 1, pp. 408–416, 2003. View at Publisher · View at Google Scholar
  100. M. D. Castellone, V. Guarino, V. De Falco et al., “Functional expression of the CXCR4 chemokine receptor is induced by RET/PTC oncogenes and is a common event in human papillary thyroid carcinomas,” Oncogene, vol. 23, no. 35, pp. 5958–5967, 2004. View at Publisher · View at Google Scholar
  101. C. L. Richard and J. Blay, “Thiazolidinedione drugs down-regulate CXCR4 expression on human colorectal cancer cells in a peroxisome proliferator activated receptor gamma-dependent manner,” International Journal of Oncology, vol. 30, no. 5, pp. 1215–1222, 2007. View at Google Scholar
  102. C. Alix-Panabières, J.-P. Brouillet, M. Fabbro et al., “Characterization and enumeration of cells secreting tumor markers in the peripheral blood of breast cancer patients,” Journal of Immunological Methods, vol. 299, no. 1-2, pp. 177–188, 2005. View at Publisher · View at Google Scholar
  103. N. Cabioglu, A. Sahin, M. Doucet et al., “Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow,” Clinical & Experimental Metastasis, vol. 22, no. 1, pp. 39–46, 2005. View at Publisher · View at Google Scholar
  104. N. J. Jordan, G. Kolios, S. E. Abbot et al., “Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells,” The Journal of Clinical Investigation, vol. 104, no. 8, pp. 1061–1069, 1999. View at Publisher · View at Google Scholar
  105. M. B. Dwinell, L. Eckmann, J. D. Leopard, N. M. Varki, and M. F. Kagnoff, “Chemokine receptor expression by human intestinal epithelial cells,” Gastroenterology, vol. 117, no. 2, pp. 359–367, 1999. View at Publisher · View at Google Scholar
  106. I. S. Zeelenberg, L. Ruuls-Van Stalle, and E. Roos, “Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma,” The Journal of Clinical Investigation, vol. 108, no. 2, pp. 269–277, 2001. View at Publisher · View at Google Scholar
  107. J.-D. Chen, X. Bai, A.-G. Yang, Y. Cong, and S.-Y. Chen, “Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy,” Nature Medicine, vol. 3, no. 10, pp. 1110–1116, 1997. View at Publisher · View at Google Scholar
  108. A. Coelho, C. Calçada, R. Catarino, D. Pinto, G. Fonseca, and R. Medeiros, “CXCL12-3 A polymorphism and lung cancer metastases protection: new perspectives in immunotherapy?” Cancer Immunology, Immunotherapy, vol. 55, no. 6, pp. 639–643, 2006. View at Publisher · View at Google Scholar
  109. B. Guleng, K. Tateishi, M. Ohta et al., “Blockade of the stromal cell-derived factor-1/CXCR4 axis attenuates in vivo tumor growth by inhibiting angiogenesis in a vascular endothelial growth factor-independent manner,” Cancer Research, vol. 65, no. 13, pp. 5864–5871, 2005. View at Publisher · View at Google Scholar
  110. H. Tamamura, A. Hori, N. Kanzaki et al., “T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer,” FEBS Letters, vol. 550, no. 1–3, pp. 79–83, 2003. View at Publisher · View at Google Scholar
  111. M. Takenaga, H. Tamamura, K. Hiramatsu et al., “A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma,” Biochemical and Biophysical Research Communications, vol. 320, no. 1, pp. 226–232, 2004. View at Publisher · View at Google Scholar
  112. T. Murakami, W. Maki, A. R. Cardones et al., “Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells,” Cancer Research, vol. 62, no. 24, pp. 7328–7334, 2002. View at Google Scholar
  113. Z. Liang, T. Wu, H. Lou et al., “Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4,” Cancer Research, vol. 64, no. 12, pp. 4302–4308, 2004. View at Publisher · View at Google Scholar
  114. I. Hashimoto, K. Koizumi, M. Tatematsu et al., “Blocking on the CXCR4/mTOR signalling pathway induces the anti-metastatic properties and autophagic cell death in peritoneal disseminated gastric cancer cells,” European Journal of Cancer, vol. 44, no. 7, pp. 1022–1029, 2008. View at Publisher · View at Google Scholar
  115. Z. Liang, Y. Yoon, J. Votaw, M. M. Goodman, L. Williams, and H. Shim, “Silencing of CXCR4 blocks breast cancer metastasis,” Cancer Research, vol. 65, no. 3, pp. 967–971, 2005. View at Google Scholar
  116. N. Lapteva, A.-G. Yang, D. E. Sanders, R. W. Strube, and S.-Y. Chen, “CXCR4 knockdown by small interfering RNA abrogates breast tumor growth in vivo,” Cancer Gene Therapy, vol. 12, no. 1, pp. 84–89, 2005. View at Publisher · View at Google Scholar
  117. J. G. Doench, C. P. Petersen, and P. A. Sharp, “siRNAs can function as miRNAs,” Genes & Development, vol. 17, no. 4, pp. 438–442, 2003. View at Publisher · View at Google Scholar
  118. D. T. Humphreys, B. J. Westman, D. I. K. Martin, and T. Preiss, “MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 47, pp. 16961–16966, 2005. View at Publisher · View at Google Scholar
  119. B. Wang, T. M. Love, M. E. Call, J. G. Doench, and C. D. Novina, “Recapitulation of short RNA-directed translational gene silencing in vitro,” Molecular Cell, vol. 22, no. 4, pp. 553–560, 2006. View at Publisher · View at Google Scholar
  120. J. Liu, M. A. Valencia-Sanchez, G. J. Hannon, and R. Parker, “MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies,” Nature Cell Biology, vol. 7, no. 7, pp. 719–723, 2005. View at Publisher · View at Google Scholar
  121. Z. Liang, H. Wu, S. Reddy et al., “Blockade of invasion and metastasis of breast cancer cells via targeting CXCR4 with an artificial microRNA,” Biochemical and Biophysical Research Communications, vol. 363, no. 3, pp. 542–546, 2007. View at Publisher · View at Google Scholar
  122. E. De Clercq, “The bicyclam AMD3100 story,” Nature Reviews Drug Discovery, vol. 2, no. 7, pp. 581–587, 2003. View at Publisher · View at Google Scholar
  123. C. W. Hendrix, C. Flexner, R. T. MacFarland et al., “Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers,” Antimicrobial Agents and Chemotherapy, vol. 44, no. 6, pp. 1667–1673, 2000. View at Publisher · View at Google Scholar
  124. S. M. Devine, N. Flomenberg, D. H. Vesole et al., “Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma,” Journal of Clinical Oncology, vol. 22, no. 6, pp. 1095–1102, 2004. View at Publisher · View at Google Scholar
  125. N. Flomenberg, S. M. Devine, J. F. DiPersio et al., “The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone,” Blood, vol. 106, no. 5, pp. 1867–1874, 2005. View at Publisher · View at Google Scholar
  126. C. W. Hendrix, A. C. Collier, M. M. Lederman et al., “Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection,” Journal of Acquired Immune Deficiency Syndromes, vol. 37, no. 2, pp. 1253–1262, 2004. View at Publisher · View at Google Scholar
  127. N. A. Lack, B. Green, D. C. Dale et al., “A pharmacokinetic-pharmacodynamic model for the mobilization of CD34+ hematopoietic progenitor cells by AMD3100,” Clinical Pharmacology & Therapeutics, vol. 77, no. 5, pp. 427–436, 2005. View at Publisher · View at Google Scholar
  128. W. C. Liles, E. Rodger, H. E. Broxmeyer et al., “Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist,” Transfusion, vol. 45, no. 3, pp. 295–300, 2005. View at Publisher · View at Google Scholar
  129. Y. Yoon, Z. Liang, X. Zhang et al., “CXC chemokine receptor-4 antagonist blocks both growth of primary tumor and metastasis of head and neck cancer in xenograft mouse models,” Cancer Research, vol. 67, no. 15, pp. 7518–7524, 2007. View at Publisher · View at Google Scholar
  130. P. C. Hermann, S. L. Huber, T. Herrler et al., “Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer,” Cell Stem Cell, vol. 1, no. 3, pp. 313–323, 2007. View at Publisher · View at Google Scholar
  131. Y. M. Li, Y. Pan, Y. Wei et al., “Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis,” Cancer Cell, vol. 6, no. 5, pp. 459–469, 2004. View at Publisher · View at Google Scholar
  132. T. Schioppa, B. Uranchimeg, A. Saccani et al., “Regulation of the chemokine receptor CXCR4 by hypoxia,” Journal of Experimental Medicine, vol. 198, no. 9, pp. 1391–1402, 2003. View at Publisher · View at Google Scholar
  133. P. Vaupel, “Tumor microenvironmental physiology and its implications for radiation oncology,” Seminars in Radiation Oncology, vol. 14, no. 3, pp. 198–206, 2004. View at Publisher · View at Google Scholar
  134. J. Blay, T. D. White, and D. W. Hoskin, “The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine,” Cancer Research, vol. 57, no. 13, pp. 2602–2605, 1997. View at Google Scholar
  135. B. B. Fredholm, G. Arslan, L. Halldner, B. Kull, G. Schulte, and W. Wasserman, “Structure and function of adenosine receptors and their genes,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 362, no. 4-5, pp. 364–374, 2000. View at Publisher · View at Google Scholar
  136. D. W. Hoskin, J. J. Butler, D. Drapeau, S. M. M. Haeryfar, and J. Blay, “Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells,” International Journal of Cancer, vol. 99, no. 3, pp. 386–395, 2002. View at Publisher · View at Google Scholar
  137. J. J. Butler, J. S. Mader, C. L. Watson, H. Zhang, J. Blay, and D. W. Hoskin, “Adenosine inhibits activation-induced T cell expression of CD2 and CD28 co-stimulatory molecules: role of interleukin-2 and cyclic AMP signaling pathways,” Journal of Cellular Biochemistry, vol. 89, no. 5, pp. 975–991, 2003. View at Publisher · View at Google Scholar
  138. E. Y. Tan, M. Mujoomdar, and J. Blay, “Adenosine down-regulates the surface expression of dipeptidyl peptidase IV on HT-29 human colorectal carcinoma cells: implications for cancer cell behavior,” The American Journal of Pathology, vol. 165, no. 1, pp. 319–330, 2004. View at Google Scholar
  139. E. Y. Tan, C. L. Richard, H. Zhang, D. W. Hoskin, and J. Blay, “Adenosine down-regulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway,” American Journal of Physiology, vol. 291, no. 3, pp. C433–C444, 2006. View at Publisher · View at Google Scholar
  140. E. Maderna, A. Salmaggi, C. Calatozzolo, L. Limido, and B. Pollo, “Nestin, PDGFRβ, CXCL12 and VEGF in glioma patients: different profiles of (pro-angiogenic) molecule expression are related with tumor grade and may provide prognostic information,” Cancer Biology & Therapy, vol. 6, no. 7, pp. 1018–1024, 2007. View at Google Scholar
  141. R. Lima e Silva, J. Shen, S. F. Hackett et al., “The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization,” The FASEB Journal, vol. 21, no. 12, pp. 3219–3230, 2007. View at Publisher · View at Google Scholar
  142. C. K. Williams, M. Segarra, M. De La Luz Sierra, R. C. A. Sainson, G. Tosato, and A. L. Harris, “Regulation of CXCR4 by the notch ligand delta-like 4 in endothelial cells,” Cancer Research, vol. 68, no. 6, pp. 1889–1895, 2008. View at Publisher · View at Google Scholar
  143. X. Hong, F. Jiang, S. N. Kalkanis et al., “SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion,” Cancer Letters, vol. 236, no. 1, pp. 39–45, 2006. View at Publisher · View at Google Scholar
  144. R. E. Bachelder, M. A. Wendt, and A. M. Mercurio, “Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4,” Cancer Research, vol. 62, no. 24, pp. 7203–7206, 2002. View at Google Scholar
  145. R. Salcedo, K. Wasserman, H. A. Young et al., “Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells. In vivo neovascularization induced by stromal-derived factor-1α,” The American Journal of Pathology, vol. 154, no. 4, pp. 1125–1135, 1999. View at Google Scholar
  146. D. Zagzag, Y. Lukyanov, L. Lan et al., “Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion,” Laboratory Investigation, vol. 86, no. 12, pp. 1221–1232, 2006. View at Publisher · View at Google Scholar
  147. Z. Liang, J. Brooks, M. Willard et al., “CXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway,” Biochemical and Biophysical Research Communications, vol. 359, no. 3, pp. 716–722, 2007. View at Publisher · View at Google Scholar
  148. D. D. Billadeau, S. Chatterjee, P. Bramati et al., “Characterization of the CXCR4 signaling in pancreatic cancer cells,” International Journal of Gastrointestinal Cancer, vol. 37, no. 4, pp. 110–119, 2006. View at Publisher · View at Google Scholar
  149. J. Wang, J. Wang, Y. Sun et al., “Diverse signaling pathways through the SDF-1/CXCR4 chemokine axis in prostate cancer cell lines leads to altered patterns of cytokine secretion and angiogenesis,” Cellular Signalling, vol. 17, no. 12, pp. 1578–1592, 2005. View at Publisher · View at Google Scholar
  150. Y.-P. Jiang, X.-H. Wu, H.-Y. Xing, and X.-Y. Du, “Role of CXCL12 in metastasis of human ovarian cancer,” Chinese Medical Journal, vol. 120, no. 14, pp. 1251–1255, 2007. View at Google Scholar
  151. M. Darash-Yahana, E. Pikarsky, R. Abramovitch et al., “Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis,” The FASEB Journal, vol. 18, no. 11, pp. 1240–1242, 2004. View at Publisher · View at Google Scholar
  152. S.-X. Yang, J.-H. Chen, X.-F. Jiang et al., “Activation of chemokine receptor CXCR4 in malignant glioma cells promotes the production of vascular endothelial growth factor,” Biochemical and Biophysical Research Communications, vol. 335, no. 2, pp. 523–528, 2005. View at Publisher · View at Google Scholar
  153. J. Kijowski, M. Baj-Krzyworzeka, M. Majka et al., “The SDF-1-CXCR4 axis stimulates VEGF secretion and activates integrins but does not affect proliferation and survival in lymphohematopoietic cells,” Stem Cells, vol. 19, no. 5, pp. 453–466, 2001. View at Publisher · View at Google Scholar
  154. D. W. Miles, L. C. Happerfield, M. S. Naylor, L. G. Bobrow, R. D. Rubens, and F. R. Balkwill, “Expression of tumour necrosis factor (TNFα) and its receptors in benign and malignant breast tissue,” International Journal of Cancer, vol. 56, no. 6, pp. 777–782, 1994. View at Publisher · View at Google Scholar
  155. J. W. Pollard, “Tumour-educated macrophages promote tumour progression and metastasis,” Nature Reviews Cancer, vol. 4, no. 1, pp. 71–78, 2004. View at Publisher · View at Google Scholar
  156. F. Balkwill, “TNF-α in promotion and progression of cancer,” Cancer and Metastasis Reviews, vol. 25, no. 3, pp. 409–416, 2006. View at Publisher · View at Google Scholar
  157. H. Kulbe, T. Hagemann, P. W. Szlosarek, F. R. Balkwill, and J. L. Wilson, “The inflammatory cytokine tumor necrosis factor-α regulates chemokine receptor expression on ovarian cancer cells,” Cancer Research, vol. 65, no. 22, pp. 10355–10362, 2005. View at Publisher · View at Google Scholar
  158. J.-W. Oh, K. Drabik, O. Kutsch, C. Choi, A. Tousson, and E. N. Benveniste, “CXC chemokine receptor 4 expression and function in human astroglioma cells,” The Journal of Immunology, vol. 166, no. 4, pp. 2695–2704, 2001. View at Google Scholar
  159. H. K. Kleinman and G. R. Martin, “Matrigel: basement membrane matrix with biological activity,” Seminars in Cancer Biology, vol. 15, no. 5, pp. 378–386, 2005. View at Publisher · View at Google Scholar
  160. C. E. Eberhart, R. J. Coffey, A. Radhika, F. M. Giardiello, S. Ferrenbach, and R. N. DuBois, “Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas,” Gastroenterology, vol. 107, no. 4, pp. 1183–1188, 1994. View at Google Scholar
  161. W. Kutchera, D. A. Jones, N. Matsunami et al., “Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 10, pp. 4816–4820, 1996. View at Publisher · View at Google Scholar
  162. J. Dimberg, A. Samuelsson, A. Hugander, and P. Söderkvist, “Differential expression of cyclooxygenase 2 in human colorectal cancer,” Gut, vol. 45, no. 5, pp. 730–732, 1999. View at Google Scholar
  163. L. T. Soumaoro, H. Uetake, T. Higuchi, Y. Takagi, M. Enomoto, and K. Sugihara, “Cyclooxygenase-2 expression: a significant prognostic indicator for patients with colorectal cancer,” Clinical Cancer Research, vol. 10, no. 24, pp. 8465–8471, 2004. View at Publisher · View at Google Scholar
  164. C. H. Liu, S.-H. Chang, K. Narko et al., “Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice,” The Journal of Biological Chemistry, vol. 276, no. 21, pp. 18563–18569, 2001. View at Publisher · View at Google Scholar
  165. S.-H. Chang, C. H. Liu, R. Conway et al., “Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 2, pp. 591–596, 2004. View at Publisher · View at Google Scholar
  166. S.-H. Chang, Y. Ai, R. M. Breyer, T. F. Lane, and T. Hla, “The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia,” Cancer Research, vol. 65, no. 11, pp. 4496–4499, 2005. View at Publisher · View at Google Scholar
  167. R. A. Gupta and R. N. DuBois, “Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2,” Nature Reviews Cancer, vol. 1, no. 1, pp. 11–21, 2001. View at Publisher · View at Google Scholar
  168. L. J. Marnett and R. N. DuBois, “COX-2: a target for colon cancer prevention,” Annual Review of Pharmacology and Toxicology, vol. 42, pp. 55–80, 2002. View at Publisher · View at Google Scholar
  169. D. Wang, J. R. Mann, and R. N. DuBois, “The role of prostaglandins and other eicosanoids in the gastrointestinal tract,” Gastroenterology, vol. 128, no. 5, pp. 1445–1461, 2005. View at Publisher · View at Google Scholar
  170. B. Rigas, I. S. Goldman, and L. Levine, “Altered eicosanoid levels in human colon cancer,” Journal of Laboratory and Clinical Medicine, vol. 122, no. 5, pp. 518–523, 1993. View at Google Scholar
  171. S. Pugh and G. A. Thomas, “Patients with adenomatous polyps and carcinomas have increased colonic mucosal prostaglandin E2,” Gut, vol. 35, no. 5, pp. 675–678, 1994. View at Publisher · View at Google Scholar
  172. R. N. DuBois, L. M. Hylind, C. R. Robinson et al., “Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients with familial adenomatous polyposis,” Digestive Diseases and Sciences, vol. 43, no. 2, pp. 311–316, 1998. View at Publisher · View at Google Scholar
  173. A. F. Badawi and M. Z. Badr, “Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ and levels of prostaglandin E2 and 15-deoxy-Δ12,14-prostaglandin J2 in human breast cancer and metastasis,” International Journal of Cancer, vol. 103, no. 1, pp. 84–90, 2003. View at Publisher · View at Google Scholar
  174. M. G. Backlund, J. R. Mann, V. R. Holla et al., “15-hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer,” The Journal of Biological Chemistry, vol. 280, no. 5, pp. 3217–3223, 2005. View at Publisher · View at Google Scholar
  175. A. S. Soydan, I. A. Tavares, P. K. Weech, N. M. Tremblay, and A. Bennett, “High molecular weight phospholipase A2 and fatty acids in human colon tumours and associated normal tissue,” European Journal of Cancer, vol. 32, no. 10, pp. 1781–1787, 1996. View at Publisher · View at Google Scholar
  176. J. Dimberg, A. Samuelsson, A. Hugander, and P. Söderkvist, “Gene expression of cyclooxygenase-2 group II and cytosolic phospholipase A2 in human colorectal cancer,” Anticancer Research, vol. 18, no. 5A, pp. 3283–3287, 1998. View at Google Scholar
  177. A. Österström, J. Dimberg, K. Fransén, and P. Söderkvist, “Expression of cytosolic and group X secretory phospholipase A2 genes in human colorectal adenocarcinomas,” Cancer Letters, vol. 182, no. 2, pp. 175–182, 2002. View at Publisher · View at Google Scholar
  178. L. Qiao, V. Kozoni, G. J. Tsioulias et al., “Selected eicosanoids increase the proliferation rate of human colon carcinoma cell lines and mouse colonocytes in vivo,” Biochimica et Biophysica Acta, vol. 1258, no. 2, pp. 215–223, 1995. View at Publisher · View at Google Scholar
  179. D. Wang, F. G. Buchanan, H. Wang, S. K. Dey, and R. N. DuBois, “Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated protein kinase cascade,” Cancer Research, vol. 65, no. 5, pp. 1822–1829, 2005. View at Publisher · View at Google Scholar
  180. A. V. Timoshenko, G. Xu, S. Chakrabarti, P. K. Lala, and C. Chakraborty, “Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells,” Experimental Cell Research, vol. 289, no. 2, pp. 265–274, 2003. View at Publisher · View at Google Scholar
  181. R. Pai, B. Soreghan, I. L. Szabo, M. Pavelka, D. Baatar, and A. S. Tarnawski, “Prostaglandin E2, transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy,” Nature Medicine, vol. 8, no. 3, pp. 289–293, 2002. View at Publisher · View at Google Scholar
  182. C. D. Funk, “Prostaglandins and leukotrienes: advances in eicosanoid biology,” Science, vol. 294, no. 5548, pp. 1871–1875, 2001. View at Publisher · View at Google Scholar
  183. L. Ermert, C. Dierkes, and M. Ermert, “Immunohistochemical expression of cyclooxygenase isoenzymes and downstream enzymes in human lung tumors,” Clinical Cancer Research, vol. 9, no. 5, pp. 1604–1610, 2003. View at Google Scholar
  184. F. A. Fitzpatrick and M. A. Wynalda, “Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro,” The Journal of Biological Chemistry, vol. 258, no. 19, pp. 11713–11718, 1983. View at Google Scholar
  185. C. Aussel, D. Mary, and M. Fehlmann, “Prostaglandin synthesis in human T cells: its partial inhibition by lectins and anti-CD3 antibodies as a possible step in T cell activation,” The Journal of Immunology, vol. 138, no. 10, pp. 3094–3099, 1987. View at Google Scholar
  186. O. Ishihara, M. H. F. Sullivan, and M. G. Elder, “Differences of metabolism of prostaglandin E2 and F2α by decidual stromal cells and macrophages in culture,” Eicosanoids, vol. 4, no. 4, pp. 203–207, 1991. View at Google Scholar
  187. A. M. Joubert, A. Panzer, P. C. Bianchi, and M.-L. Lottering, “The effects of prostaglandin A2 on cell growth, cell cycle status and apoptosis induction in HeLa and MCF-7 cells,” Cancer Letters, vol. 191, no. 2, pp. 203–209, 2003. View at Publisher · View at Google Scholar
  188. T. Yoshida, S. Ohki, M. Kanazawa et al., “Inhibitory effects of prostaglandin D2 against the proliferation of human colon cancer cell lines and hepatic metastasis from colorectal cancer,” Surgery Today, vol. 28, no. 7, pp. 740–745, 1998. View at Publisher · View at Google Scholar
  189. S. Narumiya and M. Fukushima, “Δ12-prostaglandin J2, an ultimate metabolite of prostaglandin D2 exerting cell growth inhibition,” Biochemical and Biophysical Research Communications, vol. 127, no. 3, pp. 739–745, 1985. View at Publisher · View at Google Scholar
  190. C. E. Clay, A. M. Namen, G.-I. Atsumi et al., “Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells,” Carcinogenesis, vol. 20, no. 10, pp. 1905–1911, 1999. View at Publisher · View at Google Scholar
  191. S. Kitamura, Y. Miyazaki, Y. Shinomura, S. Kondo, S. Kanayama, and Y. Matsuzawa, “Peroxisome proliferator-activated receptor γ induces growth arrest and differentiation markers of human colon cancer cells,” Japanese Journal of Cancer Research, vol. 90, no. 1, pp. 75–80, 1999. View at Google Scholar
  192. T. Shimada, K. Kojima, K. Yoshiura, H. Hiraishi, and A. Terano, “Characteristics of the peroxisome proliferator activated receptor γ (PPARγ) ligand induced apoptosis in colon cancer cells,” Gut, vol. 50, no. 5, pp. 658–664, 2002. View at Publisher · View at Google Scholar
  193. E. Mueller, M. Smith, P. Sarraf et al., “Effects of ligand activation of peroxisome proliferator-activated receptor γ in human prostate cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 20, pp. 10990–10995, 2000. View at Publisher · View at Google Scholar
  194. R. Piva, P. Gianferretti, A. Ciucci, R. Taulli, G. Belardo, and M. G. Santoro, “15-deoxy-Δ12,14-prostaglandin J2 induces apoptosis in human malignant B cells: an effect associated with inhibition of NF-κB activity and down-regulation of antiapoptotic proteins,” Blood, vol. 105, no. 4, pp. 1750–1758, 2005. View at Publisher · View at Google Scholar
  195. T. Shibata, M. Kondo, T. Osawa, N. Shibata, M. Kobayashi, and K. Uchida, “15-deoxy-Δ12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes,” The Journal of Biological Chemistry, vol. 277, no. 12, pp. 10459–10466, 2002. View at Publisher · View at Google Scholar
  196. B. M. Forman, P. Tontonoz, J. Chen, R. P. Brun, B. M. Spiegelman, and R. M. Evans, “15-deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ,” Cell, vol. 83, no. 5, pp. 803–812, 1995. View at Publisher · View at Google Scholar
  197. S. A. Kliewer, J. M. Lenhard, T. M. Willson, I. Patel, D. C. Morris, and J. M. Lehmann, “A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation,” Cell, vol. 83, no. 5, pp. 813–819, 1995. View at Publisher · View at Google Scholar
  198. B. P. Kota, T. H.-W. Huang, and B. D. Roufogalis, “An overview on biological mechanisms of PPARs,” Pharmacological Research, vol. 51, no. 2, pp. 85–94, 2005. View at Publisher · View at Google Scholar
  199. R. N. DuBois, R. Gupta, J. Brockman, B. S. Reddy, S. L. Krakow, and M. A. Lazar, “The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers,” Carcinogenesis, vol. 19, no. 1, pp. 49–53, 1998. View at Publisher · View at Google Scholar
  200. J. A. Brockman, R. A. Gupta, and R. N. DuBois, “Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells,” Gastroenterology, vol. 115, no. 5, pp. 1049–1055, 1998. View at Publisher · View at Google Scholar
  201. E. Elstner, C. Müller, K. Koshizuka et al., “Ligands for peroxisome proliferator-activated receptory and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 15, pp. 8806–8811, 1998. View at Publisher · View at Google Scholar
  202. J. Kim, P. Yang, M. Suraokar et al., “Suppression of prostate tumor cell growth by stromal cell prostaglandin D synthase-derived products,” Cancer Research, vol. 65, no. 14, pp. 6189–6198, 2005. View at Publisher · View at Google Scholar
  203. R. Grau, M. A. Iñiguez, and M. Fresno, “Inhibition of activator protein 1 activation, vascular endothelial growth factor, and cyclooxygenase-2 expression by 15-deoxy-Δ12,14-prostaglandin J2 in colon carcinoma cells: evidence for a redox-sensitive peroxisome proliferator-activated receptor-γ-independent mechanism,” Cancer Research, vol. 64, no. 15, pp. 5162–5171, 2004. View at Publisher · View at Google Scholar
  204. C. L. Richard, E. L. Lowthers, and J. Blay, “15-deoxy-Δ12,14-prostaglandin J2 down-regulates CXCR4 on carcinoma cells through PPARγ- and NFκB-mediated pathways,” Experimental Cell Research, vol. 313, no. 16, pp. 3446–3458, 2007. View at Publisher · View at Google Scholar
  205. C. Qin, R. Burghardt, R. Smith, M. Wormke, J. Stewart, and S. Safe, “Peroxisome proliferator-activated receptor γ agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor α in MCF-7 breast cancer cells,” Cancer Research, vol. 63, no. 5, pp. 958–964, 2003. View at Google Scholar
  206. J. M. Lehmann, L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer, “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ),” The Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995. View at Publisher · View at Google Scholar
  207. G. Lee, F. Elwood, J. McNally et al., “T0070907, a selective ligand for peroxisome proliferator-activated receptor γ, functions as an antagonist of biochemical and cellular activities,” The Journal of Biological Chemistry, vol. 277, no. 22, pp. 19649–19657, 2002. View at Publisher · View at Google Scholar
  208. L. M. Leesnitzer, D. J. Parks, R. K. Bledsoe et al., “Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662,” Biochemistry, vol. 41, no. 21, pp. 6640–6650, 2002. View at Publisher · View at Google Scholar
  209. T. M. Lindström and P. R. Bennett, “15-deoxy-Δ12,14-prostaglandin J2 inhibits interleukin-1β-induced nuclear factor-κB in human amnion and myometrial cells: mechanisms and implications,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 6, pp. 3534–3543, 2005. View at Publisher · View at Google Scholar
  210. T. Shiraki, N. Kamiya, S. Shiki, T. S. Kodama, A. Kakizuka, and H. Jingami, “α,β-unsaturated ketone is a core moiety of natural ligands for covalent binding to peroxisome proliferator-activated receptor γ,” The Journal of Biological Chemistry, vol. 280, no. 14, pp. 14145–14153, 2005. View at Publisher · View at Google Scholar
  211. D. S. Straus, G. Pascual, M. Li et al., “15-deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 9, pp. 4844–4849, 2000. View at Publisher · View at Google Scholar
  212. A. Rossi, P. Kapahi, G. Natoli et al., “Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase,” Nature, vol. 403, no. 6765, pp. 103–118, 2000. View at Publisher · View at Google Scholar
  213. R. Schuligoi, M. Grill, A. Heinemann, B. A. Peskar, and R. Amann, “Sequential induction of prostaglandin E and D synthases in inflammation,” Biochemical and Biophysical Research Communications, vol. 335, no. 3, pp. 684–689, 2005. View at Publisher · View at Google Scholar
  214. L. Saso, M. G. Leone, C. Sorrentino et al., “Quantification of prostaglandin D synthetase in cerebrospinal fluid: a potential marker for brain tumor,” Biochemistry & Molecular Biology International, vol. 46, no. 4, pp. 643–656, 1998. View at Publisher · View at Google Scholar
  215. C. M. Paumi, M. Wright, A. J. Townsend, and C. S. Morrow, “Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Δ12,14prostaglandin J2 in MCF7 breast cancer cells,” Biochemistry, vol. 42, no. 18, pp. 5429–5437, 2003. View at Publisher · View at Google Scholar
  216. C. M. Paumi, P. K. Smitherman, A. J. Townsend, and C. S. Morrow, “Glutathione S-transferases (GSTs) inhibit transcriptional activation by the peroxisomal proliferator-activated receptor γ (PPARγ) ligand, 15-deoxy-Δ12,14prostaglandin J2 (15-d-PGJ2),” Biochemistry, vol. 43, no. 8, pp. 2345–2352, 2004. View at Google Scholar
  217. M. J. Reginato, S. T. Bailey, S. L. Krakow et al., “A potent antidiabetic thiazolidinedione with unique peroxisome proliferator-activated receptor γ-activating properties,” The Journal of Biological Chemistry, vol. 273, no. 49, pp. 32679–32684, 1998. View at Publisher · View at Google Scholar
  218. H. S. Camp, O. Li, S. C. Wise et al., “Differential activation of peroxisome proliferator-activated receptor-γ by troglitazone and rosiglitazone,” Diabetes, vol. 49, no. 4, pp. 539–547, 2000. View at Publisher · View at Google Scholar