The alpha(2)beta(1) integrin is a metastasis suppressor in mouse models and human cancer

Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles m tumor progression and metastasis Although work in preclinical models suggests that beta(1) integrins may stimulate metastasis of a number of cancers, expression of the beta 1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients Here we have demonstrated that the alpha(2)beta(1) integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer These data are consistent with previous studies indicating high expression of alpha(2)beta(1) integrin in normal breast epithelium and loss of alpha(2)beta(1) in poorly differentiated breast cancer They are also consistent with our systematic analysis of microarray databases of human breast and prostate cancer, which revealed that decreased expression of the gene encoding alpha(2) integrin, but not genes encoding alpha(1), alpha(3), or beta(1) integrin, was predictive of metastatic dissemination and decreased survival The predictive value of alpha(2) expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status Thus, the alpha(2)beta(1) integrin functionally inhibits breast tumor metastasis, and alpha(2) expression may serve as an important biomarker of metastatic potential and patient survival