Abstract 5133: Microtentacles and invadopodia: Functionally distinct plasma membrane protrusions of metastatic breast tumor cells separated mechanistically by c-Src

Abstract

Abstract During metastasis, invading cells produce various actin-based membrane protrusions that promote directional migration and proteolysis of extracellular matrix (ECM). Our recent discovery of a filamentous actin (F-actin) component within thin tubulin-based microtentacle (McTN) protrusions in suspended MDA-MB-231 tumor cells prompted an investigation of whether these extensions are structural or functional analogs of invadopodia. We show here that MDA-MB-231s are capable of producing invadopodia and McTNs, both of which contain F-actin. Invadopodium formation was enhanced by expression of a constitutively-active c-Src kinase, and repressed by expression of dominant negative, catalytically inactive form of c-Src. In contrast expression of inactive c-Src significantly increased the McTN formation. Additionally, direct inhibition of c-Src with the SU6656 inhibitor compound significantly enhanced McTN formation, suppressed the appearance of F-actin cores and phospho-cortactin foci, and completely blocked focal degradation of extracellular matrix. These results identify McTNs and invadopodia as separate structures that provide unique and sequential contributions to metastatic progression, namely endothelial attachment and invasion, respectively. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5133.