Progestogen Inhibition of Ovarian Cancer Cell Metastasis

Summary

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

Top Publications

  1. ncbi Carcinogenic potential of ovulatory genotoxicity
    William J Murdoch
    Department of Animal Science and Reproductive Biology Program, University of Wyoming, Laramie, 82071, USA
    Biol Reprod 73:586-90. 2005
  2. pmc Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts
    William J Murdoch
    Reproductive Biology Program, University of Wyoming, Laramie, USA
    Gynecol Oncol 110:251-5. 2008
  3. ncbi Pathogenic reactions of the ovarian surface epithelium to ovulation, dimethylbenzanthracene, and estrogen are negated by vitamin E
    William J Murdoch
    Reproductive Biology Program, University of Wyoming, Laramie, Wyoming 82071, USA
    Reprod Sci 15:839-45. 2008

Scientific Experts

Detail Information

Publications3

  1. ncbi Carcinogenic potential of ovulatory genotoxicity
    William 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...
  2. pmc Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts
    William 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...
  3. ncbi Pathogenic reactions of the ovarian surface epithelium to ovulation, dimethylbenzanthracene, and estrogen are negated by vitamin E
    William 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...