The Role of Stem Cells in Ovarian Cancer: A Review

Ovarian cancer causes themost deaths amonggynecological cancers.Oneof themajor reasons for its lethality despite improved surgical techniques and improved chemotherapeutic agents in recent years is the recurrence due to chemoresistance. There have been several proposed mechanisms for chemoresistance of which the existence of cancer stem cells has recently been brought to attention. Cancer stem cells represent a small proportion of cells within a tumor with the ability to proliferate in order to increase the number of cancer stemcells, aswell as the ability to differentiate into heterogeneous-nontumorigenic cancer cell types. Also in ovarian cancer as in other types of cancer, different populations of cancer stemcells were isolated from tumors. In literature the cancer stem cells are represented by different cell populations expressing different phenotypes and characteristics. The most commonly used markers for their isolation are CD44, CD133, CD24, CD117 and ALDH, which are often used in combinations. In vitro and in vivo studies confirmed that these isolated cells behave as cancer stem cells and use different mechanisms tominimize the effect of chemotherapeutic agents. Also proteins,which are generally knownaspluripotent stemcell markers of normal stem cells, such as NANOG, OCT-4A, SOX-2 and c-MYC, have an important role in ovarian cancer development and chemoresistance. Additionally, it was demonstrated that the expression of the mentioned markers in ovarian tumors can be used as a prognostic tool, where usually the over-expression of a specificmarker correlateswith a poor prognosis. However, the conclusions of the prognostic value of cancer stem cell markers are still under debate. The reason for vague conclusions may lay in the fact that stem cells expressing the same markers can be also found in "healthy" ovaries, which could represent a bias in cancer studies. Evenmore, since stem cells located in "healthy" ovaries, including small stem cells resembling very small embryonic-like stemcells, represent themost of the cells that divide andproliferate, they seem tobe the best candidate to undergomalignant transformation andcould serve as tumor initiating cells. Therefore, the knowledgeon stemcells, expressing the pluripotency-related markers in "healthy" ovaries is a prerequisite to better understand the ovarian cancer.