Progestogen Inhibition of Ovarian Cancer Cell Metastasis
Principal Investigator: WILLIAM JAMES MURDOCH
Abstract: Common (surface) epithelial cancer of the ovary is an insidious disease with a high mortality rate. Proteolytic enzymes released from membrane vesicles have been implicated in the metastatic potential of ovarian carcinomas of surface epithelial origin. Novel results of preliminary experiments indicate that high-dose progesterone inhibits, via a receptor-independent mongenomic mechanism, secretion of urokinase plasminogen activator (uPA) by human SKOV-3 ovarian cancer cells; plasma membrane blebbing and in vitro invasive capacity were likewise attenuated. Using SKOV-3 cells as a model for ovarian carcinoma, the specific objectives of the proposed project are to characterize the dose and temporal effects of sterid hormones (progesterone, medroxyprogesterone acetate, testosterone, estradiol) on plasma membrane fluid dynamics (fluorescence polarization), enzymatic (uPA, matrix metalloproteinases) secretions, membrane morphology (to include light and transmission electron microscopic enzyme immunochemistry), in vitro (Matrigel) invasiveness, and in vivo (intraperitoneal transplantation of athymic nude mice) tumorigenes. It is predicted that responses will be selective for the lipophilic progestogens. Results from these fundamental studies may provide a basis for the prophylactic and therapeutic applications of progestogens in individuals at high-risk for the development of ovarian carcinoma and after diagnosis of early-stage disease, respectively.
Funding Period: 2002-05-01 - 2005-04-30
more information: NIH RePORT
- Carcinogenic potential of ovulatory genotoxicityWilliam J Murdoch
Department of Animal Science and Reproductive Biology Program, University of Wyoming, Laramie, 82071, USA
Biol Reprod 73:586-90. 2005..Ovarian cancer of surface epithelial origin is a deadly insidious disease because it characteristically remains asymptomatic until it has metastasized throughout the abdominal cavity; therefore, prevention is a high priority...
- Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenograftsWilliam J Murdoch
Reproductive Biology Program, University of Wyoming, Laramie, USA
Gynecol Oncol 110:251-5. 2008..That progesterone can affect susceptibility of ovarian adenocarcinoma cells and xenografts to cisplatin was tested...
- Pathogenic reactions of the ovarian surface epithelium to ovulation, dimethylbenzanthracene, and estrogen are negated by vitamin EWilliam J Murdoch
Reproductive Biology Program, University of Wyoming, Laramie, Wyoming 82071, USA
Reprod Sci 15:839-45. 2008..Acute effects of ovulation, the tumor suppressor disruptor dimethylbenzanthracene, the mitogen estradiol-17beta, and the antioxidant vitamin E on the ovarian epithelium were assessed in seasonally anestrous ewes...