| First Author | Ramirez NE | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 1 | Pages | 226-37 |
| PubMed ID | 21135504 | Mgi Jnum | J:171848 |
| Mgi Id | MGI:5000187 | Doi | 10.1172/JCI42328 |
| Citation | Ramirez NE, et al. (2011) The alphabeta integrin is a metastasis suppressor in mouse models and human cancer. J Clin Invest 121(1):226-37 |
| abstractText | 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 beta1 integrins may stimulate metastasis of a number of cancers, expression of the beta1 subunit alone has not been shown to be a useful prognostic indicator in human cancer patients. Here we have demonstrated that the alpha2beta1 integrin suppresses metastasis in a clinically relevant spontaneous mouse model of breast cancer. These data are consistent with previous studies indicating high expression of alpha2beta1 integrin in normal breast epithelium and loss of alpha2beta1 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 alpha2 integrin, but not genes encoding alpha1, alpha3, or beta1 integrin, was predictive of metastatic dissemination and decreased survival. The predictive value of alpha2 expression persisted within both good-risk and poor-risk cohorts defined by estrogen receptor and lymph node status. Thus, the alpha2beta1 integrin functionally inhibits breast tumor metastasis, and alpha2 expression may serve as an important biomarker of metastatic potential and patient survival. |
