About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 916819, 10 pages
http://dx.doi.org/10.1155/2013/916819
Review Article

Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

School of Life Sciences, The Chinese University of Hong Kong, New Territories, Hong Kong

Received 28 October 2012; Revised 13 January 2013; Accepted 14 January 2013

Academic Editor: Deepa Bhartiya

Copyright © 2013 Qinglei Zhan 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. N. Howlader, A. M. Noone, M. Krapcho, et al., SEER Cancer Statistics Review, National Cancer Institute, Bethesda, Md, USA, 1975/2009, http://seer.cancer.gov/csr/1975_2009_pops09/.
  2. A. M. Karst and R. Drapkin, “Ovarian cancer pathogenesis: a model in evolution,” Journal of Oncology, vol. 2010, Article ID 932371, 13 pages, 2010. View at Publisher · View at Google Scholar
  3. V. W. Chen, B. Ruiz, J. L. Killeen et al., “Pathology and classification of ovarian tumors,” Cancer, vol. 97, no. 10, pp. 2631–2642, 2003. View at Scopus
  4. R. C. Bast Jr., B. Hennessy, and G. B. Mills, “The biology of ovarian cancer: new opportunities for translation,” Nature Reviews Cancer, vol. 9, no. 6, pp. 415–428, 2009. View at Scopus
  5. T. Kaku, S. Ogawa, Y. Kawano et al., “Histological classification of ovarian cancer,” Medical Electron Microscopy, vol. 36, no. 1, pp. 9–17, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. R. J. Kurman and I. M. Shih, “The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory,” American Journal of Surgical Pathology, vol. 34, no. 3, pp. 433–443, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. R. J. Kurman, K. Visvanathan, R. Roden, T. C. Wu, and I. M. Shih, “Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis,” American Journal of Obstetrics and Gynecology, vol. 198, no. 4, pp. 351–356, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Kim, Y. Ueda, T. Naka, et al., “Therapeutic strategies in epithelial ovarian cancer,” Journal of Experimental & Clinical Cancer Research, vol. 31, no. 1, pp. 14–22, 2012.
  9. J. Ferlay, D. M. Parkin, and E. Steliarova-Foucher, “Estimates of cancer incidence and mortality in Europe in 2008,” European Journal of Cancer, vol. 46, no. 4, pp. 765–781, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. M. M. Leitao Jr. and D. S. Chi, “Surgical management of recurrent ovarian cancer,” Seminars in Oncology, vol. 36, no. 2, pp. 106–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. C. F. Kim and P. B. Dirks, “Cancer and stem cell biology: how tightly intertwined?” Cell Stem Cell, vol. 3, no. 2, pp. 147–150, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Ahmed, K. Abubaker, J. Findlay, et al., “Cancerous ovarian stem cells: obscure targets for therapy but relevant to chemoresistance,” Journal of Cellular Biochemistry, vol. 114, no. 1, pp. 21–34, 2013. View at Publisher · View at Google Scholar
  13. P. Valent, D. Bonnet, R. De Maria, et al., “Cancer stem cell definitions and terminology: the devil is in the details,” Nature Reviews Cancer, vol. 12, no. 11, pp. 767–775, 2012. View at Publisher · View at Google Scholar
  14. P. B. Gupta, C. L. Chaffer, and R. A. Weinberg, “Cancer stem cells: mirage or reality?” Nature Medicine, vol. 15, no. 9, pp. 1010–1012, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Kitamura, K. Okudela, T. Yazawa, H. Sato, and H. Shimoyamada, “Cancer stem cell: implications in cancer biology and therapy with special reference to lung cancer,” Lung Cancer, vol. 66, no. 3, pp. 275–281, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. K. D. Steffensen, A. B. Alvero, Y. Yang, et al., “Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer,” Journal of Oncology, vol. 2011, Article ID 620523, 12 pages, 2011. View at Publisher · View at Google Scholar
  17. M. Shibata and M. M. Shen, “The roots of cancer: stem cells and the basis for tumor heterogeneity,” BioEssays, 2012. View at Publisher · View at Google Scholar
  18. X. Wang, M. K. D. Julio, K. D. Economides et al., “A luminal epithelial stem cell that is a cell of origin for prostate cancer,” Nature, vol. 461, no. 7263, pp. 495–500, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. N. Barker and H. Clevers, “Tracking down the stem cells of the intestine: strategies to identify adult stem cells,” Gastroenterology, vol. 133, no. 6, pp. 1755–1760, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. A. K. Guddati, “Ovarian cancer stem cells: elusive targets for chemotherapy,” Medical Oncology, vol. 29, no. 5, pp. 3400–3408, 2012. View at Publisher · View at Google Scholar
  21. D. Bonnet and J. E. Dick, “Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell,” Nature Medicine, vol. 3, no. 7, pp. 730–737, 1997. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Zhang, C. Balch, M. W. Chan et al., “Identification and characterization of ovarian cancer-initiating cells from primary human tumors,” Cancer Research, vol. 68, no. 11, pp. 4311–4320, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. S. A. Bapat, A. M. Mali, C. B. Koppikar, and N. K. Kurrey, “Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer,” Cancer Research, vol. 65, no. 8, pp. 3025–3029, 2005. View at Scopus
  24. K. K. Lin and M. A. Goodell, “Purification of hematopoietic stem cells using the side population,” Methods in Enzymology, vol. 420, pp. 255–264, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. P. P. Szotek, R. Pieretti-Vanmarcke, P. T. Masiakos et al., “Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian inhibiting substance responsiveness,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 30, pp. 11154–11159, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. Q. Gao, L. Geng, G. Kvalheim, G. Gaudernack, and Z. Suo, “Identification of cancer stem-like side population cells in ovarian cancer cell line OVCAR-3,” Ultrastructural Pathology, vol. 33, no. 4, pp. 175–181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. A. G. Zeimet, D. Reimer, S. Sopper, et al., “Ovarian cancer stem cells,” Neoplasma, vol. 59, no. 6, pp. 747–755, 2012. View at Publisher · View at Google Scholar
  28. N. Ahmed, K. Abubaker, J. Findlay, and M. Quinn, “Epithelial mesenchymal transition and cancer stem cell-like phenotypes facilitate chemoresistance in recurrent ovarian cancer,” Current Cancer Drug Targets, vol. 10, no. 3, pp. 268–278, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Hu, C. McArthur, and R. B. Jaffe, “Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant,” British Journal of Cancer, vol. 102, no. 8, pp. 1276–1283, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. M. E. Anderson, “Glutathione: an overview of biosynthesis and modulation,” Chemico-Biological Interactions, vol. 111-112, pp. 1–14, 1998. View at Publisher · View at Google Scholar
  31. S. Kamazawa, J. Kigawa, Y. Kanamori et al., “Multidrug resistance gene-1 is a useful predictor of paclitaxel-based chemotherapy for patients with ovarian cancer,” Gynecologic Oncology, vol. 86, no. 2, pp. 171–176, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. D. S. Backos, C. C. Franklin, and P. Reigan, “The role of glutathione in brain tumor drug resistance,” Biochem Pharmacol, vol. 83, no. 8, pp. 1005–1012, 2012. View at Publisher · View at Google Scholar
  33. G. Jedlitschky, I. Leier, U. Buchholz, M. Center, and D. Keppler, “ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein,” Cancer Research, vol. 54, no. 18, pp. 4833–4836, 1994. View at Scopus
  34. O. M. Colvin, H. S. Friedman, M. P. Gamcsik, C. Fenselau, and J. Hilton, “Role of glutathione in cellular resistance to alkylating agents,” Advances in Enzyme Regulation, vol. 33, pp. 19–26, 1993. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Lessard and G. Sauvageau, “Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells,” Nature, vol. 423, no. 6937, pp. 255–260, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Liu, L. Cao, J. Chen et al., “Bmi1 regulates mitochondrial function and the DNA damage response pathway,” Nature, vol. 459, no. 7245, pp. 387–392, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Li, L. Y. Gong, L. B. Song et al., “Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-κB pathway,” American Journal of Pathology, vol. 176, no. 2, pp. 699–709, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. B. H. Guo, Y. Feng, R. Zhang et al., “Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer,” Molecular Cancer, vol. 10, article 10, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. E. Wang, S. Bhattacharyya, A. Szabolcs et al., “Enhancing chemotherapy response with Bmi-1 silencing in ovarian cancer,” PLoS ONE, vol. 6, no. 3, Article ID e17918, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. R. R. Wallace-Brodeur and S. W. Lowe, “Clinical implications of p53 mutations,” Cellular and Molecular Life Sciences, vol. 55, no. 1, pp. 64–75, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Fraser, T. Bai, and B. K. Tsang, “Akt promotes cisplatin resistance in human ovarian cancer cells through inhibition of p53 phosphorylation and nuclear function,” International Journal of Cancer, vol. 122, no. 3, pp. 534–546, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Y. Nikolaev, M. Li, N. Puskas, J. Qin, and W. Gu, “Parc: a cytoplasmic anchor for p53,” Cell, vol. 112, no. 1, pp. 29–40, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. M. G. Woo, K. Xue, J. Liu, et al., “Calpain-mediated processing of p53-associated parkin-like cytoplasmic protein (PARC) affects chemosensitivity of human ovarian cancer cells by promoting p53 subcellular trafficking,” The Journal of Biological Chemistry, vol. 287, no. 6, pp. 3963–3975, 2012. View at Publisher · View at Google Scholar
  44. I. Herr and K. M. Debatin, “Cellular stress response and apoptosis in cancer therapy,” Blood, vol. 98, no. 9, pp. 2603–2614, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. J. P. Gillet and M. M. Gottesman, “Mechanisms of multidrug resistance in cancer,” Methods in Molecular Biology, vol. 596, no. 1064-3745, pp. 47–76, 2010. View at Scopus
  46. R. Ernst, P. Kueppers, J. Stindt, K. Kuchler, and L. Schmitt, “Multidrug efflux pumps: substrate selection in ATP-binding cassette multidrug efflux pumps-first come, first served?” FEBS Journal, vol. 277, no. 3, pp. 540–549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. R. L. Juliano and V. Ling, “A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants,” Biochimica et Biophysica Acta, vol. 445, no. 1, pp. 152–162, 1976. View at Scopus
  48. P. Surowiak, V. Materna, I. Kaplenko et al., “ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome,” Clinical Cancer Research, vol. 12, no. 23, pp. 7149–7158, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Zhou, J. D. Schuetz, K. D. Bunting et al., “The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype,” Nature Medicine, vol. 7, no. 9, pp. 1028–1034, 2001. View at Publisher · View at Google Scholar · View at Scopus
  50. A. J. Alvi, H. Clayton, C. Joshi et al., “Functional and molecular characterisation of mammary side population cells,” Breast Cancer Research, vol. 5, no. 1, pp. R1–R8, 2003. View at Scopus
  51. S. Hosonuma, Y. Kobayashi, S. Kojo, et al., “Clinical significance of side population in ovarian cancer cells,” Human Cell, vol. 24, no. 1, pp. 9–12, 2011.
  52. A. E. van Herwaarden, E. Wagenaar, B. Karnekamp, G. Merino, J. W. Jonker, and A. H. Schinkel, “Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk,” Carcinogenesis, vol. 27, no. 1, pp. 123–130, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Aguilar-Gallardo, E. C. Rutledge, A. M. Martinez-Arroyo, et al., “Overcoming challenges of ovarian cancer stem cells: novel therapeutic approaches,” Stem Cell Reviews, vol. 8, no. 3, pp. 994–1010, 2012.
  54. P. A. Wender, W. C. Galliher, N. M. Bhat, et al., “Taxol-oligoarginine conjugates overcome drug resistance in-vitro in human ovarian carcinoma,” Gynecologic Oncology, vol. 126, no. 1, pp. 118–123, 2012.
  55. F. Arai, A. Hirao, M. Ohmura et al., “Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche,” Cell, vol. 118, no. 2, pp. 149–161, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. Y. Liu, S. E. Elf, Y. Miyata et al., “p53 regulates hematopoietic stem cell quiescence,” Cell Stem Cell, vol. 4, no. 1, pp. 37–48, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. T. Asai, Y. Liu S, S. Di Giandomenico, et al., “Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells,” Blood, vol. 120, no. 8, pp. 1601–1612, 2012. View at Publisher · View at Google Scholar
  58. H. Hock, M. J. Hamblen, H. M. Rooke et al., “Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells,” Nature, vol. 431, no. 7011, pp. 1002–1007, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Du, Y. Chen, Q. Li, et al., “HIF-1alpha deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency,” Blood, vol. 119, no. 12, pp. 2789–2798, 2012.
  60. S. Hua, X. Xiaotao, G. Renhua, et al., “Reduced miR-31 and let-7 maintain the balance between differentiation and quiescence in lung cancer stem-like side population cells,” Biomedicine & Pharmacotherapy, vol. 66, no. 2, pp. 89–97, 2012.
  61. A. M. Scott, J. D. Wolchok, and L. J. Old, “Antibody therapy of cancer,” Nature Reviews Cancer, vol. 12, no. 4, pp. 278–287, 2012.
  62. D. Burgos-Ojeda, B. R. Rueda, and R. J. Buckanovich, “Ovarian cancer stem cell markers: prognostic and therapeutic implications,” Cancer Letters, vol. 322, no. 1, pp. 1–7, 2012. View at Publisher · View at Google Scholar
  63. G. Ferrandina, G. Bonanno, L. Pierelli et al., “Expression of CD133-1 and CD133-2 in ovarian cancer,” International Journal of Gynecological Cancer, vol. 18, no. 3, pp. 506–514, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. H. Long, R. Xie, T. Xiang, et al., “Autocrine CCL5 signaling promotes invasion and migration of CD133 (+) ovarian cancer stem-like cells via NF-kappaB-mediated MMP-9 upregulation,” Stem Cells, vol. 30, no. 10, pp. 2309–2319, 2012.
  65. T. Baba, P. A. Convery, N. Matsumura et al., “Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells,” Oncogene, vol. 28, no. 2, pp. 209–218, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. L. M. Smith, A. Nesterova, M. C. Ryan, et al., “CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers,” British Journal of Cancer, vol. 99, no. 1, pp. 100–109, 2008. View at Publisher · View at Google Scholar
  67. D. Naor, R. V. Sionov, and D. Ish-Shalom, “CD44: structure, function, and association with the malignant process,” Advances in Cancer Research, vol. 71, pp. 241–319, 1997. View at Scopus
  68. R. Marhaba, P. Klingbeil, T. Nuebel, I. Nazarenko, M. W. Buechler, and M. Zoeller, “CD44 and EpCAM: cancer-initiating cell markers,” Current Molecular Medicine, vol. 8, no. 8, pp. 784–804, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. E. Meng, B. Long, P. Sullivan, et al., “CD44+/CD24- ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival,” Clinical & Experimental Metastasisdoi, vol. 29, no. 8, pp. 939–948, 2012. View at Publisher · View at Google Scholar
  70. K. H. Heider, H. Kuthan, G. Stehle, and G. Munzert, “CD44v6: a target for antibody-based cancer therapy,” Cancer Immunology, Immunotherapy, vol. 53, no. 7, pp. 567–579, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. S. C. Ghosh, S. N. Alpay, and J. Klostergaard, “CD44: a validated target for improved delivery of cancer therapeutics,” Expert Opinion on Therapeutic Targets, vol. 16, no. 7, pp. 635–650, 2012. View at Publisher · View at Google Scholar
  72. P. K. E. Börjesson, E. J. Postema, J. C. Roos et al., “Phase I therapy study with 186Re-labeled humanized monoclonal antibody BIWA 4 (Bivatuzumab) in patients with head and neck squamous cell carcinoma,” Clinical Cancer Research, vol. 9, no. 10, pp. 3961S–3972S, 2003. View at Scopus
  73. F. Casagrande, E. Cocco, S. Bellone, et al., “Eradication of chemotherapy-resistant CD44+ human ovarian cancer stem cells in mice by intraperitoneal administration of Clostridium perfringens enterotoxin,” Cancer, vol. 117, no. 24, pp. 5519–5528, 2011. View at Publisher · View at Google Scholar
  74. V. Orian-Rousseau, “CD44, a therapeutic target for metastasising tumours,” European Journal of Cancer, vol. 46, no. 7, pp. 1271–1277, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. G. Kristiansen, M. Sammar, and P. Altevogt, “Tumour biological aspects of CD24, a mucin-like adhesion molecule,” Journal of Molecular Histology, vol. 35, no. 3, pp. 255–262, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Q. Gao, Y. P. Choi, S. Kang, J. H. Youn, and N. H. Cho, “CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells,” Oncogene, vol. 29, no. 18, pp. 2672–2680, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. P. Surowiak, V. Materna, I. Kaplenko et al., “Unfavorable prognostic value of CD24 expression in sections from primary and relapsed ovarian cancer tissue,” International Journal of Gynecological Cancer, vol. 16, no. 2, pp. 515–521, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. Y. L. Choi, S. H. Kim, Y. K. Shin et al., “Cytoplasmic CD24 expression in advanced ovarian serous borderline tumors,” Gynecologic Oncology, vol. 97, no. 2, pp. 379–386, 2005. View at Publisher · View at Google Scholar · View at Scopus
  79. N. P. Bretz, A. V. Salnikov, C. Perne, et al., “CD24 controls Src/STAT3 activity in human tumors,” Cellular and Molecular Life Sciences, vol. 69, no. 22, pp. 3863–3879, 2012. View at Publisher · View at Google Scholar
  80. D. Su, H. Deng, X. Zhao et al., “Targeting CD24 for treatment of ovarian cancer by short hairpin RNA,” Cytotherapy, vol. 11, no. 5, pp. 642–652, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Miettinen and J. Lasota, “KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation,” Applied Immunohistochemistry and Molecular Morphology, vol. 13, no. 3, pp. 205–220, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. S. A. Bapat, A. M. Mali, C. B. Koppikar, and N. K. Kurrey, “Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer,” Cancer Research, vol. 65, no. 8, pp. 3025–3029, 2005. View at Scopus
  83. L. Luo, J. Zeng, B. Liang et al., “Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome,” Experimental and Molecular Pathology, vol. 91, no. 2, pp. 596–602, 2011. View at Publisher · View at Google Scholar · View at Scopus
  84. M. R. Raspollini, G. Amunni, A. Villanucci, G. Baroni, A. Taddei, and G. L. Taddei, “c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study,” Annals of Oncology, vol. 15, no. 4, pp. 594–597, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. W. K. Chau, C. K. Ip, A. S. Mak, et al., “c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/beta-catenin-ATP-binding cassette G2 signaling,” Oncogene, 2012. View at Publisher · View at Google Scholar
  86. R. J. Schilder, M. W. Sill, R. B. Lee et al., “Phase II evaluation of imatinib mesylate in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a gynecologic oncology group study,” Journal of Clinical Oncology, vol. 26, no. 20, pp. 3418–3425, 2008. View at Publisher · View at Google Scholar · View at Scopus
  87. B. B. Patel, Y. A. He, X. M. Li et al., “Molecular mechanisms of action of imatinib mesylate in human ovarian cancer: a proteomic analysis,” Cancer Genomics and Proteomics, vol. 5, no. 3-4, pp. 137–150, 2008. View at Scopus
  88. S. Imrich, M. Hachmeister, and O. Gires, “EpCAM and its potential role in tumor-initiating cells,” Cell Adhesion & Migration, vol. 6, no. 1, pp. 30–38, 2012.
  89. C. Pauli, M. Münz, C. Kieu et al., “Tumor-specific glycosylation of the carcinoma-associated epithelial cell adhesion molecule EpCAM in head and neck carcinomas,” Cancer Letters, vol. 193, no. 1, pp. 25–32, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. M. J. E. M. Gosens, L. C. L. Van Kempen, C. J. H. Van De Velde, J. H. J. M. Van Krieken, and I. D. Nagtegaal, “Loss of membranous Ep-CAM in budding colorectal carcinoma cells,” Modern Pathology, vol. 20, no. 2, pp. 221–232, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. P. A. Baeuerle and O. Gires, “EpCAM (CD326) finding its role in cancer,” British Journal of Cancer, vol. 96, no. 3, pp. 417–423, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. J. P. Thiery, H. Acloque, R. Y. J. Huang, and M. A. Nieto, “Epithelial-mesenchymal transitions in development and disease,” Cell, vol. 139, no. 5, pp. 871–890, 2009. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Sebastian, A. Kuemmel, M. Schmidt, and A. Schmittel, “Catumaxomab: a bispecific trifunctional antibody,” Drugs of Today, vol. 45, no. 8, pp. 589–597, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Seimetz, H. Lindhofer, and C. Bokemeyer, “Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM×anti-CD3) as a targeted cancer immunotherapy,” Cancer Treatment Reviews, vol. 36, no. 6, pp. 458–467, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. S. A. Marchitti, C. Brocker, D. Stagos, and V. Vasiliou, “Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily,” Expert Opinion on Drug Metabolism and Toxicology, vol. 4, no. 6, pp. 697–720, 2008. View at Publisher · View at Google Scholar · View at Scopus
  96. C. N. Landen Jr., B. Goodman, A. A. Katre et al., “Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer,” Molecular Cancer Therapeutics, vol. 9, no. 12, pp. 3186–3199, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. Y. T. Saw, J. Yang, S. K. Ng, et al., “Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures,” BMC Cancer, vol. 12, article 329, 2012. View at Publisher · View at Google Scholar
  98. I. A. Silva, S. Bai, K. McLean et al., “Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival,” Cancer Research, vol. 71, no. 11, pp. 3991–4001, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Liu, S. Brown, T. Goktug, et al., “Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells,” British Journal of Cancer, vol. 107, no. 9, pp. 1488–1497, 2010.
  100. M. Khanna, C. H. Chen, A. Kimble-Hill, et al., “Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases,” The Journal of Biological Chemistry, vol. 286, no. 50, pp. 43486–43494, 2011.
  101. S. Peng, N. J. Maihle, and Y. Huang, “Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer,” Oncogene, vol. 29, no. 14, pp. 2153–2159, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. P. T. Masiakos, D. T. MacLaughlin, S. Maheswaran et al., “Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS,” Clinical Cancer Research, vol. 5, no. 11, pp. 3488–3499, 1999. View at Scopus
  103. X. Wei, D. Dombkowski, K. Meirelles et al., “Müllerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 44, pp. 18874–18879, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. S. Sell, “Stem cell origin of cancer and differentiation therapy,” Critical Reviews in Oncology/Hematology, vol. 51, no. 1, pp. 1–28, 2004. View at Publisher · View at Google Scholar · View at Scopus
  105. G. Yin, A. B. Alvero, V. Craveiro, et al., “Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential,” Oncogene, vol. 32, no. 1, pp. 39–49, 2013. View at Publisher · View at Google Scholar
  106. A. K. Jain, K. Allton, M. Iacovino, et al., “p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells,” PLoS Biology, vol. 10, no. 2, Article ID e1001268, 2012.
  107. Z. Yu, Y. Li, H. Fan, et al., “miRNAs regulate stem cell self-renewal and differentiation,” Frontiers in Genetics, vol. 3, pp. 191–195, 2012.
  108. L. J. Gudas and J. A. Wagner, “Retinoids regulate stem cell differentiation,” Journal of Cellular Physiology, vol. 226, no. 2, pp. 322–330, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. Y. C. Lim, H. J. Kang, Y. S. Kim, et al., “All-trans-retinoic acid inhibits growth of head and neck cancer stem cells by suppression of Wnt/beta-catenin pathway,” European Journal of Cancer, vol. 48, no. 17, pp. 3310–3318, 2012. View at Publisher · View at Google Scholar
  110. S. L. Soignet, F. Benedetti, A. Fleischauer et al., “Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia,” Leukemia, vol. 12, no. 10, pp. 1518–1521, 1998. View at Scopus
  111. J. M. Whitworth, A. I. Londono-Joshi, J. C. Sellers, et al., “The impact of novel retinoids in combination with platinum chemotherapy on ovarian cancer stem cells,” Gynecologic Oncology, vol. 125, no. 1, pp. 226–230, 2012.
  112. A. Ruiz-Vela, C. Aguilar-Gallardo, A. M. Martinez-Arroyo, et al., “Specific unsaturated fatty acids enforce the transdifferentiation of human cancer cells toward adipocyte-like cells,” Stem Cell Reviews, vol. 7, no. 4, pp. 898–909, 2011. View at Publisher · View at Google Scholar
  113. A. Ruiz-Vela, C. Aguilar-Gallardo, and C. Simón, “Building a framework for embryonic microenvironments and cancer stem cells,” Stem Cell Reviews and Reports, vol. 5, no. 4, pp. 319–327, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. H. J. Li, F. Reinhardt, H. R. Herschman, et al., “Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling,” Cancer Discovery, vol. 2, no. 9, pp. 840–855, 2012. View at Publisher · View at Google Scholar
  115. R. Lis, C. Touboul, C. M. Raynaud, et al., “Mesenchymal cell interaction with ovarian cancer cells triggers pro-metastatic properties,” PLoS One, vol. 7, no. 5, Article ID e38340, 2012. View at Publisher · View at Google Scholar
  116. E. Katz, K. Skorecki, and M. Tzukerman, “Niche-dependent tumorigenic capacity of malignant ovarian ascites-derived cancer ceil subpopulations,” Clinical Cancer Research, vol. 15, no. 1, pp. 70–80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  117. D. Liang, Y. Ma, J. Liu, et al., “The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells,” BMC Cancer, vol. 12, pp. 201–211, 2012. View at Publisher · View at Google Scholar
  118. M. A. LaBarge, “The difficulty of targeting cancer stem cell niches,” Clinical Cancer Research, vol. 16, no. 12, pp. 3121–3129, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. D. P. Bartel, “MicroRNAs: target recognition and regulatory functions,” Cell, vol. 136, no. 2, pp. 215–233, 2009.
  120. I. Lavon, D. Zrihan, A. Granit et al., “Gliomas display a microRNA expression profile reminiscent of neural precursor cells,” Neuro-Oncology, vol. 12, no. 5, pp. 422–433, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. M. T. M. van Jaarsveld, J. Helleman, E. M. J. J. Berns, and E. A. C. Wiemer, “MicroRNAs in ovarian cancer biology and therapy resistance,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 8, pp. 1282–1290, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. C. X. Xu, M. Xu, L. Tan, et al., “MicroRNA MiR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog,” The Journal of Biological Chemistry, vol. 287, no. 42, pp. 34970–34978, 2012. View at Publisher · View at Google Scholar
  123. W. Cheng, T. Liu, X. Wan, et al., “MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells,” The FEBS Journal, vol. 279, no. 11, pp. 2047–2059, 2012. View at Publisher · View at Google Scholar
  124. Q. Wu, R. Guo, M. Lin, B. Zhou, and Y. Wang, “MicroRNA-200a inhibits CD133/1+ ovarian cancer stem cells migration and invasion by targeting E-cadherin repressor ZEB2,” Gynecologic Oncology, vol. 122, no. 1, pp. 149–154, 2011. View at Publisher · View at Google Scholar · View at Scopus
  125. F. H. Sarkar, Y. Li, Z. Wang, D. Kong, and S. Ali, “Implication of microRNAs in drug resistance for designing novel cancer therapy,” Drug Resistance Updates, vol. 13, no. 3, pp. 57–66, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. X. Zhong, N. Li, S. Liang, Q. Huang, G. Coukos, and L. Zhang, “Identification of microRNAs regulating reprogramming factor LIN28 in embryonic stem cells and cancer cells,” Journal of Biological Chemistry, vol. 285, no. 53, pp. 41961–41971, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. B. Fendler and G. Atwal, “Systematic deciphering of cancer genome networks,” Yale Journal of Biology and Medicine, vol. 85, no. 3, pp. 339–345, 2012.
  128. A. J. Williamson and A. D. Whetton, “The requirement for proteomics to unravel stem cell regulatory mechanisms,” Journal of Cellular Physiology, vol. 226, no. 10, pp. 2478–2483, 2011. View at Publisher · View at Google Scholar · View at Scopus
  129. V. Vathipadiekal, D. Saxena, S. C. Mok, et al., “Identification of a potential ovarian cancer stem cell gene expression profile from advanced stage papillary serous ovarian cancer,” PLoS One, vol. 7, no. 1, pp. 1–12, 2012.