Progestogen Inhibition of Ovarian Cancer Cell Metastasis

描述(申请人提供)：常见的(表面)上皮癌 卵巢是一种潜伏性疾病，死亡率高。蛋白水解酶 从膜泡释放的酶与肿瘤的转移有关。 表面上皮源性卵巢癌的潜在性。新的结果： 初步实验表明，大剂量黄体酮通过一种 尿激酶型纤溶酶原分泌的受体非依赖性单体机制 人卵巢癌SKOV-3细胞激活因子(UPA)；质膜 起泡和体外侵袭能力也同样减弱。使用SKOV-3 细胞作为卵巢癌的模型，其具体目标是 拟议的项目是描述类固醇的剂量和时间效应 激素(孕酮、甲羟孕酮醋酸酯、睾酮、雌二醇) 关于质膜流体动力学(荧光偏振)、酶(uPA， 基质金属蛋白酶)分泌物、膜形态(含光 和透射电子显微镜酶免疫化学)，在体外 (Matrigel)侵袭性和体内(腹膜内移植 裸鼠)致癌。据预测，反应将是 对亲脂的促孕素有选择性。从这些基本原理中得出的结果 研究可能为其预防和治疗应用提供依据。 卵巢发育高危人群孕激素水平的研究 分别为癌症和确诊后的早期疾病。

DESCRIPTION (provided by applicant): 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.