Integrins α5β1, αvβ1, and αvβ6 Collaborate in Squamous Carcinoma Cell Spreading and Migration on Fibronectin

Abstract

The expression of αvβ6 fibronectin/tenascin receptor integrin is induced in malignant transformation of oral epithelium. In this study, we demonstrate the contribution of αvβ6 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 αvβ6 integrin on 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 αvβ6 integrin. In addition to αvβ6, all 3 cell lines expressed α5β1 and αvβ1 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 αvβ6, however, was not used as a primary but as an alternative fibronectin receptor by SCC cells, as the inhibitory anti-β6 integrin antibody alone had no effect on spreading. In migration, however, αvβ6, α5β1, and αvβ1 integrins were all used in cooperation. The presence of αvβ1 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.