Initial remodeling of the tumor microenvironment is mediated by tumor cells, Cav1-positive CAFs and other stromal cells such as bone marrow-derived cells. Deposition and modification of ECM by these cells in combination with other environmental cues including hypoxia and TGF-β induces EMT, facilitating tumor invasion. As EMT is induced in tumor cells, they form feed forward signaling loops by further remodeling the tumor microenvironment by secreting a variety of factors including LOX, TGF-β, Tenascin-C, and POSTN. Furthermore, EMT results in the modulation of the expression of discoidin domain receptors DDR1 and DDR2, affecting tumor cell responses to the ECM.