αvβ6 integrin upregulates matrix metalloproteinase 9 and promotes migration of normal oral keratinocytes

The integrin alphav beta6 is a fibronectin receptor that is undetectable on normal keratinocytes in situ, but is increased significantly in wound healing and in culture-established keratinocytes, suggesting that it may promote changes associated with cell motility. Using normal human oral keratinocytes we have shown that cultured cells express relatively high levels of alphav beta6 and this integrin has a functional role in both cell adhesion and migration towards fibronectin. We provide experimental evidence that the increased expression of alphav beta6 by normal human oral keratinocytes results in coordinate changes, which promote a more migratory phenotype. Thus increased expression of alphav beta6 results in a fibronectin-dependent increase in pro-matrix metalloproteinase 9, matrix metalloproteinase 9 activity increases normal human oral keratinocyte migration, and this may be further dependent on plasmin activation. The results suggest a key role for alphav beta6 in these processes and indicate a coordinated link between alphav beta6 expression and upregulation of matrix metalloproteinase 9. It appears that alphav beta6 may function in normal human oral keratinocyte migration through matrix-metallo-proteinase-9-dependent and -independent mechanisms.