Abstract LB-253: Mesenchymal stem cells of fallopian tube cancers are specifically attracted by mature ovulating follicles: implication of fallopian tube origin of serous ovarian carcinoma

Background: Recent studies of surgical specimens resected from carriers of breast ovarian cancer syndrome have suggested a fallopian tube origin of serous carcinoma of the ovary. We tested the following hypothesis: Cancer initiating cells arising from fallopian tube home to ovulation wound via chemotaxis of follicular fluid. Materials and Methods: Mesenchymal stem cells from fallopian tube cancers (FTC-MSC) and normal fallopian tubes (FT-MSC) were respectively culture-isolated from two patients with FIGO stage 3C serous adenocarcinoma of fallopian tube and three patients with uterine myoma. Tissues were digested with collagenase type I and dispase and cells were grown in anti-oxidant DMEM medium containing 5% fetal bovine serum. Characteristics of stem cells including cell surface markers, colony formation, trans-differentiation and hTERT expression were analyzed. Follicular fluids and cells were procured and cultured from ovulating women receiving in-vitro fertilization program. Chemotaxis and cell migration activities were studied by trans-well migration assay and wound healing assay. Results: The isolated FTC-MSC had a doubling time of around 25h and gave a typical mesenchymal stem cell phenotypes with anchorage independent growth, lack of gap junction communication, positive for CD24, CD44, CD133, CD29, CD90, CD56, CD117 and CD146, negative for CD 34 and CD45, and had high hTERT expression. Capabilities of osteogenic and adipogenic differentiation and chemo-resistence paclitaxol and cisplatin were evident. FTC-MSC but not FT-MSC highly responded to mature, ovulating follicular fluid, and to condition media of cultured follicular cells or ovarian stromas, and much less to those derived from immature follicles, and to conditional media of endometrial, cervical and peritoneal cells in culture. Conclusions: The highly specific chmotaxic effect of mature, ovulating follicles to FTC-MSC supports the hypothesis of fallopian tube origin of serous ovarian carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-253.