Fibronectin and its alpha 5 beta 1 integrin receptor in malignancy.

Fibronectin and the alpha 5 beta 1 integrin play complex roles in malignancy. While normal cells usually deposit a fibronectin matrix around themselves, malignant cell lines often fail to do so. Decreased expression of the alpha 5 beta 1 integrin, which directs fibronectin matrix deposition, is one of the reasons for deficient matrix deposition. The defect can be corrected by expression of additional alpha 5 beta 1 from transfected cDNAs and exacerbated by selecting cells for loss of all alpha 5 beta 1. Tumorigenicity is suppressed in the alpha 5 beta 1 overexpressors and enhanced in the alpha 5 beta 1-negative cells. Synthetic peptides that bind to the alpha 5 beta 1 and other integrins can modulate their functions and suppress malignancy and metastasis in vivo. The signaling mechanisms that underlie these tumor-suppressive effects of the fibronectin matrix and the integrins are an important target for ongoing study.