Macrophage-dependent tumor cell transendothelial migration is mediated by Notch1/MenaINV-initiated invadopodium formation

• DOI: 10.1038/srep37874
• Publication Date: 2016-11-30T11:13:14Z
• Authors: Jeanine Pignatelli; Jose Javier Bravo...; Minna Roh-Johnson; Saumil J. Gandhi; Yarong Wang; Xiaoming Chen; Robert J. Eddy; Alice Xue; Robert H. Singer; Louis Hodgson; Maja H. Oktay; John S. Condeelis
• Keywords: Intravasation; Podosome; Invadopodia

Abstract The process of intravasation involving transendothelial migration is a key step in metastatic spread. How the triple cell complex composed macrophage, Mena over-expressing tumor and endothelial cell, called microenvironment metastasis (TMEM), facilitates not completely understood. Previous work has shown that physical contact between macrophage results formation invadopodia, actin-rich matrix degrading protrusions, important for invasion dissemination. Herein, we show macrophage-induced invadopodium formed through Notch1/Mena INV signaling pathway upon contact. This heterotypic – interaction upregulation activation MENA transcription. Notch1 expression are required migration, necessary during intravasation. Inhibition Notch blocked vitro dissemination cells from primary vivo . Our findings indicate novel role regulation provide mechanistic information essential to use therapeutic inhibitors metastasis.