Ovarian cancer is the fourth leading cause of cancer death among U.S. women and has the highest mortality rate of all gynecologic cancers. Lysophosphatidic acid presents in high concentration in ascites fluid and is a potent ovarian cancer growth factor. Phospholipase A2 (PLA2) is a LPA generating enzyme and presents in ascites fluid. PLA2 has been shown to correlate with the malignant stage of several cancers. The hypotheses tested is that PLA2-II is a disease progressive marker for ovarian cancer and a rate-limiting enzyme in LPA production and a therapeutic target for ovarian cancer. To test these hypotheses, the following specific aims will have to be accomplished: 1) to investigate whether type Il PL,A2 level Is correlated with advanced stages of ovarian cancer; 2) to investigate whether PLA2-II is a rate-limiting enzyme in production of LPA; and 3) to Investigate whether inhibition of PLA2-II will decrease LPA production In ascites fluid and retard tumor growth In ovarian cancer bearing mice. Completion of these studies will provide insight into the role of PLA2-II In LPA production and ovarian tumor growth. If the hypotheses hold true, prognosis and therapeutic treatment for ovarian cancer can be greatly improved and thousands of patients with ovarian cancer can benefit from this research. PROPOSED COMMERCIAL APPLICATION: Ovarian cancer diagnostic and therapeutic applications.
