Abstract C78: Integrin αvβ3 drives stemness in the pregnant and neoplastic mammary gland

Abstract

Abstract Carcinoma cell expression of the integrin αvβ3 is associated with enhanced tumorigenicity and metastasis in a diverse array of human tumors. Here, we reveal αvβ3 expression in a subset of CD44+CD24-/low cancer stem cells in human breast tumor biopsies. In fact, αvβ3 is both necessary and sufficient to account for stem-like properties in breast tumor cells, suggesting that αvβ3 may contribute to mammary stem (MaSC)/progenitor cell behavior. While αvβ3 is a luminal progenitor marker in the virgin murine mammary gland, we noted a dramatic, but transient, increase in αvβ3 levels that defined the mammary stem cell pool at mid-pregnancy. Genetic deletion of β3 surprisingly had no effect on luminal progenitor behavior or ductal morphogenesis. In contrast, β3 was specifically required for MaSC clonogenicity and alveologenesis at mid-pregnancy, yet had no influence on MaSCs in the virgin gland. These findings reveal an unexpected role for αvβ3 in driving mammary stemness during pregnancy that may be related to the stem-like properties, and high metastatic potential associated with αvβ3 expression in human breast cancers. Citation Format: Jay Desgrosellier, Jacqueline Lesperance, Laetitia Seguin, David Cheresh. Integrin αvβ3 drives stemness in the pregnant and neoplastic mammary gland. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C78.