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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 485156, 8 pages
http://dx.doi.org/10.1155/2012/485156
Review Article

CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth

Centre de Recherche, Centre Hospitalier, Faculté de Pharmacie l’Université de Montréal et Institut du Cancer de Montréal, Montréal, QC, Canada H2L 4M1

Received 19 June 2012; Accepted 5 July 2012

Academic Editor: Karen M. Dwyer

Copyright © 2012 Bertrand Allard et al. 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. I. Mellman, G. Coukos, and G. Dranoff, “Cancer immunotherapy comes of age,” Nature, vol. 480, no. 7378, pp. 480–489, 2011. View at Publisher · View at Google Scholar
  2. J. Galon, F. Pagès, F. M. Marincola, et al., “The immune score as a new possible approach for the classification of cancer,” Journal of Translational Medicine, vol. 10, article 1, 2012.
  3. B. Mlecnik, M. Tosolini, A. Kirilovsky et al., “Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction,” Journal of Clinical Oncology, vol. 29, no. 6, pp. 610–618, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Galluzzi, L. Senovilla, L. Zitvogel, and G. Kroemer, “The secret ally: immunostimulation by anticancer drugs,” Nature Reviews Drug Discovery, vol. 11, no. 3, pp. 215–233, 2012. View at Publisher · View at Google Scholar
  5. Y. Ma, L. Aymeric, C. Locher et al., “Contribution of IL-17-producing γδ T cells to the efficacy of anticancer chemotherapy,” Journal of Experimental Medicine, vol. 208, no. 3, pp. 491–503, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Stagg, S. Loi, U. Divisekera et al., “Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 17, pp. 7142–7147, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Robert, L. Thomas, I. Bondarenko et al., “Ipilimumab plus dacarbazine for previously untreated metastatic melanoma,” New England Journal of Medicine, vol. 364, no. 26, pp. 2517–2526, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. S. L. Topalian, F. S. Hodi, J. R. Brahmer et al., “Safety, activity, and immune correlates of anti-PD-1 antibody in cancer,” New England Journal of Medicine, vol. 366, no. 26, pp. 2443–2454, 2012. View at Publisher · View at Google Scholar
  9. J. R. Brahmer, S. S. Tykodi, L. Q. M. Chow et al., “Safety and activity of anti-PD-L1 antibody in patients with advanced cancer,” New England Journal of Medicine, vol. 366, no. 26, pp. 2455–2465, 2012. View at Publisher · View at Google Scholar
  10. J. Stagg and M. J. Smyth, “Extracellular adenosine triphosphate and adenosine in cancer,” Oncogene, vol. 29, no. 39, pp. 5346–5358, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. D. G. Shirley, R. M. Vekaria, and J. Sévigny, “Ectonucleotidases in the kidney,” Purinergic Signalling, vol. 5, no. 4, pp. 501–511, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Henttinen, S. Jalkanen, and G. G. Yegutkin, “Adherent leukocytes prevent adenosine formation and impair endothelial barrier function by ecto-5-nucleotidase/CD73-dependent mechanism,” Journal of Biological Chemistry, vol. 278, no. 27, pp. 24888–24895, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. T. Eckle, T. Krahn, A. Grenz et al., “Cardioprotection by ecto-5-nucleotidase (CD73) and A2B adenosine receptors,” Circulation, vol. 115, no. 12, pp. 1581–1590, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. M. R. Elliott, F. B. Chekeni, P. C. Trampont et al., “Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance,” Nature, vol. 461, no. 7261, pp. 282–286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Zitvogel, O. Kepp, L. Galluzzi, and G. Kroemer, “Inflammasomes in carcinogenesis and anticancer immune responses,” Nature Immunology, vol. 13, no. 4, pp. 343–351, 2012. View at Publisher · View at Google Scholar
  16. B. B. Fredholm, A. P. IJzerman, K. A. Jacobson, J. Linden, and C. E. Müller, “International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update,” Pharmacological Reviews, vol. 63, no. 1, pp. 1–34, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Serra, A. L. Horenstein, T. Vaisitti et al., “CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death,” Blood, vol. 118, no. 23, pp. 6141–6152, 2011. View at Publisher · View at Google Scholar
  18. L. Bavaresco, A. Bernardi, E. Braganhol et al., “The role of ecto-5 nucleotidase/CD73 in glioma cell line proliferation,” Molecular and Cellular Biochemistry, vol. 319, no. 1-2, pp. 61–68, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. R. Sadej, J. Spychala, and A. C. Skladanowski, “Expression of ecto-5-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma,” Melanoma Research, vol. 16, no. 3, pp. 213–222, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Spychala, E. Lazarowski, A. Ostapkowicz, L. H. Ayscue, A. Jin, and B. S. Mitchell, “Role of estrogen receptor in the regulation of ecto-5-nucleotidase and adenosine in breast cancer,” Clinical Cancer Research, vol. 10, no. 2, pp. 708–717, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. M. J. Haas, “CD73: double-breasted suit, SciBX: Science-Business eXchange 3,” 2010.
  22. K. Synnestvedt, G. T. Furuta, K. M. Comerford et al., “Ecto-5-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia,” Journal of Clinical Investigation, vol. 110, no. 7, pp. 993–1002, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. X. Li, T. Zhou, X. Zhi, F. Zhao, L. Yin, and P. Zhou, “Effect of hypoxia/reoxygenation on CD73 (ecto-5-nucleotidase) in mouse microvessel endothelial cell lines,” Microvascular Research, vol. 72, no. 1-2, pp. 48–53, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. G. L. Semenza, “Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning,” Biochimica et Biophysica Acta, vol. 1813, no. 7, pp. 1263–1268, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. H. K. Eltzschig, J. C. Ibla, G. T. Furuta et al., “Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endotheliumml: role of ectonucleotidases and adenosine A 2B receptors,” Journal of Experimental Medicine, vol. 198, no. 5, pp. 783–796, 2003. View at Publisher · View at Google Scholar · View at Scopus
  26. H. K. Eltzschig, D. Kö hler, T. Eckle, T. Kong, S. C. Robson, and S. P. Colgan, “Central role of Sp1-regulated CD39 in hypoxia/ischemia protection,” Blood, vol. 113, no. 1, pp. 224–232, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Spychala, A. G. Zimmermann, and B. S. Mitchell, “Tissue-specific regulation of the ecto-5-nucleotidase promoter. Role of the cAMP response element site in mediating repression by the upstream regulatory region,” Journal of Biological Chemistry, vol. 274, no. 32, pp. 22705–22712, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Spychala and J. Kitajewski, “Wnt and β-catenin signaling target the expression of ecto-5-nucleotidase and increase extracellular adenosine generation,” Experimental Cell Research, vol. 296, no. 2, pp. 99–108, 2004. View at Publisher · View at Google Scholar
  29. P. Polakis, “Wnt signaling and cancer,” Genes and Development, vol. 14, no. 15, pp. 1837–1851, 2000. View at Scopus
  30. H. Wang, S. Lee, C. Lo Nigro et al., “NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity,” British Journal of Cancer, vol. 106, no. 8, pp. 1446–1452, 2012. View at Publisher · View at Google Scholar
  31. P. A. Beavis, J. Stagg, P. K. Darcy, and M. J. Smyth, “CD73: a potent suppressor of antitumor immune responses,” Trends in Immunology, vol. 33, no. 5, pp. 231–237, 2012. View at Publisher · View at Google Scholar
  32. X.-R. Wu, X.-S. He, Y.-F. Chen, et al., “High expression of CD73 as a poor prognostic biomarker in human colorectal cancer,” Journal of Surgical Oncology, vol. 106, no. 2, pp. 130–137, 2012.
  33. R. Leth-Larsen, R. Lund, H. V. Hansen et al., “Metastasis-related plasma membrane proteins of human breast cancer cells identified by comparative quantitative mass spectrometry,” Molecular and Cellular Proteomics, vol. 8, no. 6, pp. 1436–1449, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Supernat, A. Markiewicz, B. Seroczyńska et al., “CD73 expression as a potential marker of good prognosis in breast carcinoma,” Applied Immunohistochemistry and Molecular Morphology, vol. 20, no. 2, pp. 103–107, 2012. View at Publisher · View at Google Scholar
  35. S. Deaglio, K. M. Dwyer, W. Gao et al., “Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression,” Journal of Experimental Medicine, vol. 204, no. 6, pp. 1257–1265, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. F. S. Regateiro, D. Howie, K. F. Nolan et al., “Generation of anti-inflammatory adenosine byleukocytes is regulated by TGF-β,” European Journal of Immunology, vol. 41, no. 10, pp. 2955–2965, 2011. View at Publisher · View at Google Scholar
  37. G. Borsellino, M. Kleinewietfeld, D. Di Mitri et al., “Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression,” Blood, vol. 110, no. 4, pp. 1225–1232, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Mandapathil, B. Hilldorfer, M. J. Szczepanski et al., “Generation and accumulation of immunosuppressive adenosine by human CD4+CD25 high FOXP3+ regulatory T Cells,” Journal of Biological Chemistry, vol. 285, no. 10, pp. 7176–7186, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. S. P. Hilchey, J. J. Kobie, M. R. Cochran et al., “Human follicular lymphoma CD39+-infiltrating T cells contribute to adenosine-mediated T cell hyporesponsiveness,” Journal of Immunology, vol. 183, no. 10, pp. 6157–6166, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. K. M. Dwyer, D. Hanidziar, P. Putheti et al., “Expression of CD39 by human peripheral blood CD4+CD25+ T cells denotes a regulatory memory phenotype,” American Journal of Transplantation, vol. 10, no. 11, pp. 2410–2420, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Romio, B. Reinbeck, S. Bongardt, S. Hüls, S. Burghoff, and J. Schrader, “Extracellular purine metabolism and signaling of CD73-derived adenosine in murine treg and teff cells,” American Journal of Physiology, vol. 301, no. 2, pp. C530–C539, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Chalmin, G. Mignot, M. Bruchard et al., “Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression,” Immunity, vol. 36, no. 3, pp. 362–373, 2012. View at Publisher · View at Google Scholar
  43. P. E. Zarek, C. T. Huang, E. R. Lutz et al., “A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells,” Blood, vol. 111, no. 1, pp. 251–259, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. J. Stagg, U. Divisekera, H. Duret et al., “CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis,” Cancer Research, vol. 71, no. 8, pp. 2892–2900, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. L. Wang, J. Fan, L. F. Thompson et al., “CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice,” Journal of Clinical Investigation, vol. 121, no. 6, pp. 2371–2382, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. G. G. Yegutkin, F. Marttila-Ichihara, M. Karikoski et al., “Altered purinergic signaling in CD73-deficient mice inhibits tumor progression,” European Journal of Immunology, vol. 41, no. 5, pp. 1231–1241, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Mandapathil, M. J. Szczepanski, M. Szajnik et al., “Increased ectonucleotidase expression and activity in regulatory T cells of patients with head and neck cancer,” Clinical Cancer Research, vol. 15, no. 20, pp. 6348–6357, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. M. Mandapathil, M. J. Szczepanski, M. Szajnik et al., “Adenosine and prostaglandin e2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells,” Journal of Biological Chemistry, vol. 285, no. 36, pp. 27571–27580, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Jalkanen and M. Salmi, “VAP-1 and CD73, endothelial cell surface enzymes in leukocyte extravasation,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 28, no. 1, pp. 18–26, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Ålgars, M. Karikoski, G. G. Yegutkin et al., “Different role of CD73 in leukocyte trafficking via blood and lymph vessels,” Blood, vol. 117, no. 16, pp. 4387–4393, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Takedachi, D. Qu, Y. Ebisuno et al., “CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes,” Journal of Immunology, vol. 180, no. 9, pp. 6288–6296, 2008. View at Scopus
  52. A. Zernecke, K. Bidzhekov, B. Özüyaman et al., “CD73/Ecto-5-nucleotidase protects against vascular inflammation and neointima formation,” Circulation, vol. 113, no. 17, pp. 2120–2127, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. J. H. Mills, L. F. Thompson, C. Mueller et al., “CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 27, pp. 9325–9330, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. C. S. Hilaire, C. Shira, S. G. Ziegler et al., “NT5E mutations and arterial calcifications,” New England Journal of Medicine, vol. 364, no. 5, pp. 432–442, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. H. K. Eltzschig, L. F. Thompson, J. Karhausen et al., “Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism,” Blood, vol. 104, no. 13, pp. 3986–3992, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. P. F. Lennon, C. T. Taylor, G. L. Stahl, and S. P. Colgan, “Neutrophil-derived 5'-adenosine monophosphate promotes endothelial barrier function via CD73-mediated conversion to adenosine and endothelial A(2B) receptor activation,” Journal of Experimental Medicine, vol. 188, no. 8, pp. 1433–1443, 1998. View at Publisher · View at Google Scholar · View at Scopus
  57. T. Kong, K. A. Westerman, M. Faigle, H. K. Eltzschig, and S. P. Colgan, “HIF-dependent induction of adenosine A2B receptor in hypoxia,” FASEB Journal, vol. 20, no. 13, pp. 2242–2250, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Ryzhov, J. L. McCaleb, A. E. Goldstein, I. Biaggioni, and I. Feoktistov, “Role of adenosine receptors in the regulation of angiogenic factors and neovascularization in hypoxia,” Journal of Pharmacology and Experimental Therapeutics, vol. 320, no. 2, pp. 565–572, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. I. Feoktistov, A. E. Goldstein, S. Ryzhov et al., “Differential expression of adenosine receptors in human endothelial cells: role of A2B receptors in angiogenic factor regulation,” Circulation Research, vol. 90, no. 5, pp. 531–538, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Ahmad, S. Ahmad, L. Glover et al., “Adenosine A2A receptor is a unique angiogenic target of HIF-2α in pulmonary endothelial cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 26, pp. 10684–10689, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Desai, C. Victor-Vega, S. Gadangi, M. C. Montesinos, C. C. Chu, and B. N. Cronstein, “Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1,” Molecular Pharmacology, vol. 67, no. 5, pp. 1406–1413, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. N. S. Umapathy, Z. Fan, E. A. Zemskov, I. B. Alieva, S. M. Black, and A. D. Verin, “Molecular mechanisms involved in adenosine-induced endothelial cell barrier enhancement,” Vascular Pharmacology, vol. 52, no. 5-6, pp. 199–206, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Narravula, P. F. Lennon, B. U. Mueller, and S. P. Colgan, “Regulation of endothelial CD73 by adenosine: paracrine pathway for enhanced endothelial barrier function,” Journal of Immunology, vol. 165, no. 9, pp. 5262–5268, 2000. View at Scopus
  64. J. Niemelä, T. Henttinen, G. G. Yegutkin et al., “IFN-α induced adenosine production on the endotheliumml: a mechanism mediated by CD73 (ecto-5-nucleotidase) up-regulation,” Journal of Immunology, vol. 172, no. 3, pp. 1646–1653, 2004. View at Scopus
  65. J. Niemelä, I. Ifergan, G. G. Yegutkin, S. Jalkanen, A. Prat, and L. Airas, “IFN-β regulates CD73 and adenosine expression at the blood-brain barrier,” European Journal of Immunology, vol. 38, no. 10, pp. 2718–2726, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. N. D. Khoa, M. C. Montesinos, A. J. Williams, M. Kelly, and B. N. Cronstein, “Th1 cytokines regulate adenosine receptors and their downstream signaling elements in human microvascular endothelial cells,” Journal of Immunology, vol. 171, no. 8, pp. 3991–3998, 2003. View at Scopus
  67. K. Kalsi, C. Lawson, M. Dominguez, P. Taylor, M. H. Yacoub, and R. T. Smolenski, “Regulation of ecto-5-nucleotidase by TNF-α in human endothelial cells,” Molecular and Cellular Biochemistry, vol. 232, no. 1-2, pp. 113–119, 2002. View at Publisher · View at Google Scholar · View at Scopus
  68. L. Airas, J. Niemela, and S. Jalkanen, “CD73 engagement promotes lymphocyte binding to endothelial cells via a lymphocyte function-associated antigen-1-dependent mechanism,” Journal of Immunology, vol. 165, no. 10, pp. 5411–5417, 2000. View at Scopus
  69. L. Airas, J. Niemelä, M. Salmi, T. Puurunen, D. J. Smith, and S. Jalkanen, “Differential regulation and function of CD73, a glycosyl- phosphatidylinositol-linked 70-kD adhesion molecule, on lymphocytes and endothelial cells,” Journal of Cell Biology, vol. 136, no. 2, pp. 421–431, 1997. View at Publisher · View at Google Scholar · View at Scopus
  70. N. Sethi and Y. Kang, “Unravelling the complexity of metastasis—molecular understanding and targeted therapies,” Nature Reviews Cancer, vol. 11, no. 10, pp. 735–748, 2011. View at Publisher · View at Google Scholar
  71. H. Lee, E. C. K. Lin, L. Liu, and J. W. Smith, “Gene expression profiling of tumor xenografts: in vivo analysis of organ-specific metastasis,” International Journal of Cancer, vol. 107, no. 4, pp. 528–534, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Stagg, P. A. Beavis, U. Divisekera et al., “CD73-deficient mice are resistant to carcinogenesis,” Cancer Research, vol. 72, no. 9, pp. 2190–2196, 2012. View at Publisher · View at Google Scholar
  73. J. Stagg, U. Divisekera, N. McLaughlin et al., “Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 4, pp. 1547–1552, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. 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 · View at Scopus
  75. E. C. Woodhouse, D. F. Amanatullah, J. A. Schetz, L. A. Liotta, M. L. Stracke, and T. Clair, “Adenosine receptor mediates motility in human melanoma cells,” Biochemical and Biophysical Research Communications, vol. 246, no. 3, pp. 888–894, 1998. View at Publisher · View at Google Scholar · View at Scopus
  76. P. Zhou, X. Zhi, T. Zhou et al., “Overexpression of ecto-5-nucleotidase (CD73) promotes T-47D human breast cancer cells invasion and adhesion to extracellular matrix,” Cancer Biology and Therapy, vol. 6, no. 3, pp. 426–431, 2007. View at Scopus
  77. L. Wang, X. Zhou, T. Zhou et al., “Ecto-5-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells,” Journal of Cancer Research and Clinical Oncology, vol. 134, no. 3, pp. 365–372, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. X. Zhi, S. Chen, P. Zhou et al., “RNA interference of ecto-5-nucleotidase (CD73) inhibits human breast cancer cell growth and invasion,” Clinical and Experimental Metastasis, vol. 24, no. 6, pp. 439–448, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. B. M. Künzli, M. I. Bernlochner, S. Rath et al., “Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer,” Purinergic Signalling, vol. 7, no. 2, pp. 231–241, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Ohta, E. Gorelik, S. J. Prasad et al., “A2A adenosine receptor protects tumors from antitumor T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13132–13137, 2006. View at Publisher · View at Google Scholar · View at Scopus
  81. D. Jin, J. Fan, L. Wang et al., “CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression,” Cancer Research, vol. 70, no. 6, pp. 2245–2255, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. X. Zhou, X. Zhi, P. Zhou et al., “Effects of ecto-5-nucleotidase on human breast cancer cell growth in vitro and in vivo.,” Oncology Reports, vol. 17, no. 6, pp. 1341–1346, 2007. View at Scopus
  83. F. Ghiringhelli, L. Apetoh, A. Tesniere et al., “Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors,” Nature Medicine, vol. 15, no. 10, pp. 1170–1178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. L. Aymeric, L. Apetoh, F. Ghiringhelli et al., “Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity,” Cancer Research, vol. 70, no. 3, pp. 855–858, 2010. View at Publisher · View at Google Scholar · View at Scopus