Isolation And Identification Of Cancer Stem/Progenitor Cell In Ovarian Cancer And The Study Of Anti-CD44 Molecules Can Remodel It’s The Biology Behaviors

Recently, new concepts have been proposed on the critical implication of cancer stem cells (CSCs) also designated as tumourigenic cancer progenitor cells or cancer-initiating cells, in cancer initiation and development, metastasis and resistance to conventional therapies. Many cancers seem to be maintained by a hierarchical organization that includes slowly dividing stem cells, rapidly dividing transit amplifying cells (precursor cells) and differentiated cells. Unfortunately traditional means show anergy to these so-called cancer stem/progenitor cells. So new anti-tumor strategies aim at modifying the biology behaviors of these tumor stem/progenitor cells need to be explored. Using anti-CD44 antibody as a potential strategy in targeting leukemia stem cells (LSCs) is being extensively studied. In ovarian cancer, the most lethal malignancy of the female reproductive system, concept on cancer stem cells has also been emerging. But whether anti-CD44 monoclonal antibody has effects on such subpopulation in ovarian cancer is still unknown and necessary to be explored. Therefore, in our present study, we first isolated and identified human ovarian cancer cells with stem/progenitor properties from SKOV-3, a well-established cell line, and then used A3D8, one widely-used anti-CD44 monoclonal antibody, against all CD44 isoforms, to treat the so-called ovarian cancer stem/progenitor cells, to value the potential effects of anti-CD44 monoclonal antibody on the major biology behaviors of this subpopulation. The result showed that the existence of a small subpopulation that have so-called "stemness"in SKOV-3 cell line and can be propagated and used as a tool for the study of ovarian cancer stem cells; and we found that against this subpopulation with "sternness" A3D8 could①inhibit cell proliferation in dose-dependent manner;②decrease the percentage of G0/G1 with increasing percentage of S and G2/M phase;③enhance the cisplatin-induced apoptosis;④inhibit the clone-formation efficiency;⑤induce the expression of CK7 and CA125;⑥inhibit the invasive efficiency. Based on these findings, we suggested that human primary ovarian cancer stem/progenitor cells derived from a subpopulation of SKOV-3, a well-established cell line, have properties of self-renewal capabilities, pluripotential differentiation and indefinite proliferation. And importantly, the cells are more tumorigenic than SK-OV-3. Furthermore, anti-CD44 molecules can remodel the biology behaviors of human ovarian cancer cells with stem/progenitor property. In this regard, our study provided valuable evidence for the targeting therapy of this malignancy.