Fibronectin-binding integrins alpha-v-beta6 and alpha9beta1 drive TGF-beta independent directional migration of head and neck carcinoma collectives through fibroblast-derived matrix

For a tumor to develop and spread, the growth-repressive environment of the host tissue must undergo profound changes. These include dramatic modifications in the molecular composition and architecture of the extracellular matrix (ECM) and altered integrin expression in cancer cells to allow productive interactions. An overwhelming proportion of histopathologically invasive carcinomas, including HNSCC, retain an epithelial phenotype at invading tumor fronts. Local adhesion-dependent signals at the tumor-stroma interface can govern the different modes that tumor cells adopt to invade surrounding stroma. Defining the nature and organization of the tumor ECM and the adhesive interactions that promote cancer cell invasion is of utmost importance for tailoring effective therapies to control locoregional expansion and metastatic dissemination.