Abstract 615: Apigenin regulates prostate cancer matrix composition and cell attachment through an integrin alpha 1 dependent pathway

Abstract

Abstract Prostate cancer (PCa) mortality is primarily attributed to metastatic rather than primary, organ-confined disease. Acquiring a motile and invasive phenotype is an important step in the development of metastasis. This step involves remodeling of the extracellular matrix (ECM) and of cell-matrix interactions, cell movement mediated by the actin cytoskeleton, and activation of focal adhesion kinase (FAK)/Src signaling. Epidemiologic studies suggest that the metastatic behavior of PCa may be an ideal target for chemoprevention. The natural flavone apigenin is known to have chemopreventive properties against many cancers, including PCa. Building upon our previous findings showing that apigenin inhibits cell motility and invasion of PCa cells through the FAK/Src signaling pathway, here we study the effect of apigenin on integrin receptors, cell attachment, and ECM composition. By using an alpha/beta integrin-mediated cell adhesion array, we found that integrin alpha 1 (ITGA1) was the only integrin subunit to be down-regulated by apigenin in PC3-M cells. ITGA1, whose only binding partner is integrin beta 1, is a receptor for collagen and laminin. Integrin α1α1 gives cells the ability to attach to collagenous substrata. As collagen and laminin are important regulators of PCa cell survival, growth and metastasis to bone, we next elucidated the effect of apigenin on PC3-M cell attachment to laminin 1 and collagen IV. We found that apigenin decreases cell attachment to both of these ECM molecules, suggesting a potential anti-tumorigenic mechanism. It has been shown that integrin α1α1 can regulate the synthesis of collagen. So we next tested whether apigenin can alter the ECM deposited by PC3-M cells. We first tested whether ECM deposited by apigenin-treated cells provided the same adhesive support to PCa cells as the ECM deposited by the untreated cells. Interestingly, even cells not treated with apigenin did not attach and spread well on the ECM deposited by apigenin-treated cells, indicating that apigenin treatment changes the composition of the ECM. Using Western blot to evaluate differences in the composition of matrix deposited by control cells and apigenin-treated cells, we found that apigenin-treated cells produce much less collagen I and IV, thus correlating with the decrease in adhesion and spreading. These results demonstrate that the chemopreventive bioflavonoid apigenin may inhibit PCa cell adhesion through a combined effect on integrin α1α1 cell surface expression and ECM deposition. 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 615. doi:1538-7445.AM2012-615