Cancer stem cells and ovarian cancer
Characteristics, importance and potential applicationsin clinical practice

Czech version

Authors: L. Záveský ¹; E. Jandáková ²; M. Kohoutová ¹
Authors‘ workplace: Ústav biologie a lékařské genetiky 1. LF UK a VFN, Praha, přednostka doc. MUDr. M. Kohoutová, CSc. ¹; Ústav patologie LF MU a FN, Brno, přednosta doc. MUDr. J. Feit, CSc. ²
Published in: Ceska Gynekol 2013; 78(2): 169-174

Overview

Ovarian cancer is the most malignant and the second most common gynecological cancer which encompasses a heterogeneous group of tumors with a different etiology. Extra-ovarian tissues may play a role in the development of ovarian cancer, despite this issue is still debated. This disease is associated with a strong chemoresistance and tendency to recurrence, and asymptomatic behaviour at early stages. Effective screening markers have not been established yet. Cancer stem cells have been postulated to play a role within tumor formation and by the establishment of chemotherapy-resistant population of malignant cells after the surgery and application of chemotherapy. These cells are multipotent cells capable of un-limited divisions and have potential to induce tumorigenesis in immune-suppressed mice. Their detailed characterization is still an open issue, however there have been identified several markers associated with ovarian cancer stem cells. The major markers of ovarian cancer stem cells identified so far are CD133, ALDH, CD44, CD117, CD24 and EpCAM. Their occurrence in primary tumors may be associated with patients´prognosis; however there are insufficient data for definite conclusions. Dynamic processes of carcinogenesis result also in changes of cancer stem cells phenotypes based on the microenvironmental changes within the tumor. The markers may thus be acquired, or lost, as it has been proven experimentally. As regards the possibility to use targeted, specific therapy approaches, there are some promising studies, suggesting this may be a method of potential treatment. Further characterization and functional studies of cancer stem cells will be necessary for the elucidation of carcinogenesis, chemoresistance and metastases formation-associated processes. Such studies will be the basis for establishment of novel diagnostic, prognostic and therapeutic approaches for the ovarian cancer treatment. The most recent results on ovarian cancer stem cells research are presented in this paper.

Keywords:
ovarian cancer – diagnostics – treatment – cancer stem cells – CD133 – ALDH – CD44 – CD24 – CD117 – EpCAM

Sources

1. Záveský, L., Jančárková, N., Kohoutová, M. Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease. Neoplasma, 2011, 58, p. 457–468.

2. Záveský, L. Karcinom ovaria – na cestě k lepší diagnostice a léčbě. Inter Med, 2011, 13, 12, s. 490–492.

3. Fischerová, D., Zikán, M., Pinkavová, I., et al. Předoperační diagnostika ovariálních nádorů. Onkologie, 2012, 6, 2, s. 59–64.

4. Záveský, L. CA125/MUC16 jako diagnostický a prognostický marker pro karcinom ovaria. Onkologie, 2012, 6, 2, s. 65–67.

5. Záveský, L., Jandáková, E., Kohoutová, M. MikroRNA a jejich potenciál v diagnostice karcinomu ovaria. Současný stav a možná budoucnost. Prakt Gyn, 2012, 16, 2–4, s. 59–65.

6. Klát, J. Primární chirurgická léčba karcinomu ovaria. Onkologie, 2012, 6, 2, s. 71–73.

7. Burgos-Ojeda, D., Rueda, BR., Buckanovich, RJ. Ovarian cancer stem cell markers: Prognostic and therapeutic implications. Cancer Lett, 2012, 322, p. 1–7.

8. Choi, YP., Shim, HS., Gao, MQ., et al. Molecular portraits of intratumoral heterogeneity in human ovarian cancer. Cancer Lett, 2011, 307, p. 62–71.

9. Medema, JP., Vermeulen, L. Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature, 2011, 474, p. 318–326.

10. Steg, AD., Bevis, KS., Katre, AA., et al. Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res, 2012, 18, p. 869–881.

11. Kryczek, I., Liu, SL., Roh, M., et al. Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer, 2012,130, p. 29–39.

12. Ferrandina, G., Bonanno, G., Pierelli, L., et al. Expression of CD133-1 and CD133-2 in ovarian cancer. Int J Gyn Cancer, 2008, 18, p. 506–514.

13. Baba, T., Convery, PA., Matsumura, N., et al. Epigenetic regulation of CD133 and tumorigenicity of CD133+ovarian cancer cells. Oncogene, 2009, 28, p. 209–218.

14. Curley, MD., Therrien, VA., Cummings, CL., et al. CD133 Expression Defines a Tumor Initiating Cell Population in Primary Human Ovarian Cancer. Stem Cells, 2009, 27, p. 2875–2883.

15. Zhang, S., Balch, C., Chan, MW., et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res, 2008, 68, p. 4311–4320.

16. Silva, IA., Bai, SM., McLean, K., et al. Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res, 2011, 71, p. 3991–4001.

17. Landen, CN., Goodman, B., Katre, AA., et al. Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther, 2010, 9, p. 3186–3199.

18. Wang, YC., Yo, YT., Lee, HY., et al. ALDH1-Bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. Am J Pathol, 2012, 180, p. 1159–1169.

19. Hou, NY., Yang, K., Chen, T., et al. CD133(+)CD44(+) subgroups may be human small intestinal stem cells. Mol Biol Rep, 2011, 38, p. 997–1004.

20. Cheng, WW., Liu, T., Wan, XP., et al. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J, 2012, 279, p. 2047–2059.

21. Meirelles, K., Benedict, LA., Dombkowski, D., et al. Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance. Proc Natl Acad Sci USA, 2012, 109, p. 2358–2363.

22. Jaggupilli, A., Elkord, E. Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol, 2012, Article ID 708036.

23. Luo, LJ., Zeng, JF., Liang, B., et al. Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol, 2011, 91, p. 596–602.

24. Gao, MQ., Choi, YP., Kang, S., et al. CD24(+) cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene, 2010, 29, p. 2672–2680.

25. Choi, YP., Shim, HS., Gao, MQ., et al. Molecular portraits of intratumoral heterogeneity in human ovarian cancer. Cancer Lett, 2011, 307, p. 62–71.

26. Patriarca, C., Macchi, RM., Marschner, AK., Mellstedt, H. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev, 2012, 38, p. 68–75.

27. Wei, XL., Dombkowski, D., Meirelles, K., et al. Müllerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc Natl Acad Sci USA, 2010, 107, p. 18874–18879.

28. Zhang, J., Guo, XQ., Chang, DY., et al. CD133 expression associated with poor prognosis in ovarian cancer. Mod Pathol, 2012, 25, p. 456–464.

29. Steffensen, KD., Alvero, AB., Yang, Y., et al. Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer. J Oncol, 2011, 2011, 620523.

30. Green, JM., Alvero, AB., Kohen, F., Mor, G. 7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine A novel compound capable of inducing cell death in epithelial ovarian cancer stem cells. Cancer Biol Ther, 2009, 8, p. 1747–1753.