Abstract 9: An angiogenic function for E-cadherin in ovarian cancer

Abstract

Abstract The loss of E-cadherin, a cell-cell adhesion molecule, is a well-established marker for metastasis of cancer. Although E-cadherin is synthesized as a transmembrane molecule, it can be cleaved of the ectodomain and released in a soluble form (sE-cad), and this accounts a key mechanism for a rapid reduction of functional E-cadherin at the cell surface. Yet, very little is known about how this important protein dictates the metastasis of these tumors. In ovarian cancer, a highly metastatic tumor that is rapidly lethal, sE-cad is highly expressed in the serum and metastatic ascites of ovarian carcinoma patients. Despite many studies focused on the role of E-cadherin loss in weakening cell-cell adhesion, whether sE-cad has biological activity in itself remain virtually unknown. Here we show for the first time that sE-cad can transduce angiogenic signals. sE-cad was also present in the culture supernatant of ovarian cancer lines. sE-cad of supernatant and a recombinant sE-cad-Fc chimera potently stimulated the migration of, permeability, and tubulogenesis by human umbilical vein endothelial cells in vitro. sE-cad also promoted functional neovascularization in a Matrigel implant model in vivo. These effects could be reversed by neutralizing anti-sE-cad, confirming that the effects were sE-cad specific. In addition, we found that sE-cad bound to VE-cadherin, an effect mediated through the phosphatidylinositol 3-kinase/Akt-β-catenin pathway. These results unravel a new and important piece to the complex biology of tumor angiogenesis and metastasis, and provide insights of novel mechanisms regulating angiogenesis (This study was supported by RGC grant HKU781013). Citation Format: Maggie Kei Shuen Tang, Alice Sze Tsai Wong. An angiogenic function for E-cadherin in ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 9. doi:10.1158/1538-7445.AM2014-9