Membrane type-1 matrix metalloproteinase (MT1-MMP) processing of pro-α v integrin regulates cross-talk between α vβ 3 and α 2β 1 integrinsin breast carcinoma cells

Abstract

We have recently demonstrated that in breast carcinoma MCF7 cells MT1-MMP processes the α v, α 3, and α 5 integrin precursors generating the respective mature S-S-linked heavy and light α-chains. The precursor of α 2 integrin subunit was found resistant to MT1-MMP proteolysis. The processing of the α v subunit by MT1-MMP facilitated α vβ 3-dependent adhesion, activation of FAK signaling pathway, and migration of MCF7 cells on vitronectin. To elucidate further the effects of MT1-MMP on cellular integrins, we examined the functional activity of α 5β 1 and α 2β 1 integrins in MCF7 cells expressing MT1-MMP. Either expression of MT1-MMP alone or its coexpression with α vβ 3 failed to affect the functionality of α 5β 1 integrin, and adhesion of cells to fibronectin. MT1-MMP, however, profoundly affected the cross-talk involving α vβ 3 and α 2β 1 integrins. In MT1-MMP-deficient cells, integrin α vβ 3 suppressed the functional activity of the collagen-binding α 2β 1 integrin receptor and diminished cell adhesion to type I collagen. Coexpression of MT1-MMP with integrin α vβ 3 restored the functionality of α 2β 1 integrin and, consequently, the ability of MCF7 cells to adhere efficiently to collagen. We conclude that the MT1-MMP-controlled cross-talk between α vβ 3 and α 2β 1 integrins supports binding of aggressive, MT1-MMP-, and α vβ 3 integrin-expressing malignant cells on type I collagen, the most common substratum of the extracellular matrix.