Abstract 397: LPA promotes ovarian cancer mesothelial invasion by regulating VCAM-1 expression

Abstract

Abstract Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single cell layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5 yr survival <25%). Lysophosphatidic acid (LPA) is abundant in malignant ascites where it regulates ovarian cancer cell growth, migration and response to chemotherapy. Using a cell culture model system of mesothelial invasion, treatment with a LPA receptor antagonist resulted in a dose-dependent decrease in mesothelial invasion. Eliminating LPA1 expression in mesothelial cells using siRNA blocked mesothelial invasion (70% inhibition relative to control) and resulted in decreased expression of VCAM-1. We have shown previously that VCAM-1 is expressed preferentially on the mesothelium of ovarian cancer patients where it regulates mesothelial invasion and ovarian cancer metastatic progression. Re-expression of VCAM-1 in mesothelial cells lacking LPA1 expression rescued mesothelial invasion. Together, these observations implicate a role for LPA in modulating the tumor microenvironment to regulate ovarian cancer progression. Furthermore, they specifically point to a role for LPA in the regulation of VCAM-1 expression in ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 397. doi:10.1158/1538-7445.AM2011-397