The α2β1 integrin is a metastasis suppressor in mouse models and human cancer

Abstract

Integrins regulate cell-cell and cell-matrix adhesion and thereby play critical roles in tumor progression and metastasis. Although work in preclinical models suggests that β₁ integrins may stimulate metastasis of a number of cancers, expression of the β₁ subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the α₂β₁ integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of α₂β₁ integrin in normal breast epithelium and loss of α₂β₁ 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 α₂ integrin, but not genes encoding α₁, α₃, or β₁ integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of α₂ expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the α₂β₁ integrin functionally inhibits breast tumor metastasis, and α₂ expression may serve as an important biomarker of metastatic potential and patient survival.