The Integrins α5β1 and α2β1 Enhance Cell Motility

Abstract

Cell migration through connective tissue, or cell invasion, is a fundamental biomechanical process during metastasis formation. Cell invasion usually requires cell adhesion to the extracellular matrix through integrins. In some tumors, increased integrin expression is associated with increased malignancy and metastasis formation. Here, we studied the invasion of cancer cells with different α5β1 and α2β1 integrin expression levels into 3D collagen fiber matrices. Using a cell sorter, we isolated α5β1high and α5β1low as well as α2β1high and α2β1low expressing sub cell lines from parental MDA-MB-231 breast cancer cells. α5β1high and α2β1high cells showed increased cell invasiveness compared to α5β1low and α2β1low cells, respectively. Similar results were obtained for 786-O kidney and T24 bladder carcinoma cells, and in cells in which the α5 integrin subunit was knocked down using specific siRNA. Knock-down of the collagen receptor integrin subunits α2 did also reduce invasiveness, but to a lesser degree compared to the integrin subunit α5. Fourier transform traction microscopy revealed that the α5β1high cells generated 7-fold larger contractile forces compared to α5β1low cells. Cell invasiveness was reduced after addition of the myosin light chain kinase inhibitor ML-7 in α5β1high cells, but not in α5β1low cells, suggesting that α5β1 integrins enhance cell invasion through enhanced transmission and generation of contractile forces.