Integrins α5β1, αvβ1, and αvβ6 collaborate in squamous carcinoma cell spreading and migration on fibronectin

The expression of alpha v beta 6 fibronectin/tenascin receptor integrin is induced in malignant transformation of oral epithelium. In this study, we demonstrate the contribution of alpha v beta 6 as well as other fibronectin receptor integrins in squamous cell carcinoma (SCC) cell adhesion and migration. Of 11 SCC cell lines isolated from the head and neck area, 8 (73%) expressed alpha v beta 6 integrin an the cell surface. Three cell lines were chosen for further functional experiments: 1 with relatively high, 1 with moderate, and 1 with minimal surface expression of alpha v beta 6 integrin. In addition to alpha v beta 6, all 3 cell lines expressed alpha 5 beta 1 and alpha v beta 1 fibronectin receptor integrins. Function-blocking experiments with inhibitory anti-integrin antibodies showed that all these three integrins were functional in SCC cell spreading on fibronectin. Integrin alpha v beta 6, however, was not used as a primary but as an alternative fibronectin receptor by SCC cells, as the inhibitory anti-beta 6 integrin antibody alone had no effect on spreading. In migration, however; alpha v beta 6, alpha 5 beta 1, and alpha v beta 1 integrins were all used in cooperation. The presence of alpha v beta 1 integrin in SCC cells is a novel finding as is its contribution to SCC cell migration. When one or two of these three receptors were blocked, the cells demonstrated an adaptive ability to remain migratory using integrins that were not targeted by antibodies. Utilization of a combination of receptors of different affinities may be beneficial for SCC cell migration versatility. (C) 2000 Academic Press.