Alternatively-Activated Macrophages Upregulate Mesothelial Expression of P-Selectin to Enhance Adhesion of Ovarian Cancer Cells.

ABSTRACT: Peritoneal metastasis of high-grade serous ovarian cancer (HGSOC) occurs when tumor cells suspended in ascites adhere to mesothelial cells. Despite the strong relationship between metastatic burden and prognosis in HGSOC, there are currently no therapies specifically targeting the metastatic process. We utilized a coculture model and multivariate analysis to examine how interactions between tumor cells, mesothelial cells, and alternatively-activated macrophages (AAM) influence the adhesion of tumor cells to mesothelial cells. We found that AAM-secreted MIP-1β activates CCR5/PI3K signaling in mesothelial cells, resulting in expression of P-selectin on the mesothelial cell surface. Tumor cells attached to this de novo P-selectin through CD24, resulting in increased tumor cell adhesion

SUBMITTER: Carroll MJ 

PROVIDER: S-EPMC6030435 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature