Abstract 4613: A role of integrin-associated CD151 in human ovarian cancer

Abstract

Abstract Despite being implicated in multiple types of human epithelia-origin cancer, laminin-binding (LB) integrins (e.g., α3α1 and α6β4) have rarely been investigated for their roles in human ovarian tumors. More recently, we and others have shown that CD151, a member of the tetraspanin family, not only forms tight surface complexes with these adhesion receptors, but also mediates the malignancy of human carcinomas largely in a LB integrin-dependent manner. Here we report our studies on the role of CD151 in human ovarian cancer. Initially, we stained human ovarian tumor tissue microarrays with CD151-specific antibody. Our data showed that the majority of ovarian tumors exhibited a reduced expression of CD151 protein, compared to the fallopian tube, implying a putative suppressing role of this tetraspanin in ovarian cancer. With this hint we next evaluated the impact of CD151 ablation on the behaviors and proliferation of cultured human ovarian cancer cells. While CD151 removal had a minimal impact on cell motility or invasion, it markedly enhanced cell proliferation. Also, CD151-deficeint cells appeared to have reduced cell-cell contacts, suggestive of epithelial-mesenchymal transition (EMT)-like changes. However, there was no dramatic difference in the surface expression of E-cadherin protein, according to our FACS analyses. To substantiate these observations, we also injected ovarian cancer cells with or without CD151 knockdown into immuno-deficient nude mice subcutaneously or orthotopically (intra-peritoneal). Results from these ex vivo analyses showed that disruption of CD151 accelerated ovarian tumor growth and production of ascites fluid in mice, further supporting a role of CD151 in ovarian tumor progression. While tumors in the control group had homogenous epithelial-like appearance, those derived from CD151-ablated cells exhibited mucin-related vacuoles and diverse morphologies. Our subsequent DNA array and protein analyses indicated that there was indeed a marked increase in the expression of a mucin family member in CD151-deficient tumor cells. Collectively, these results provide strong evidence that CD151 suppresses human ovarian cancer progression by regulating tumor cell proliferation and extracellular microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4613. doi:1538-7445.AM2012-4613