alpha v beta 6 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 heal ing and in culture-established keratinocytes, suggesting that it may promot e changes associated with cell motility. Using normal human oral keratinocy tes we have shown that cultured cells express relatively high levels of alp hav beta6 and this integrin has a functional role in both cell adhesion and migration towards fibronectin. We provide experimental evidence that the i ncreased expression of alphav beta6 by normal human oral keratinocytes resu lts in coordinate changes, which promote a more migratory phenotype. Thus i ncreased expression of alphav beta6 results in a fibronectin-dependent incr ease in pro-matrix metalloproteinase 9, matrix metalloproteinase 9 activity increases normal human oral keratinocyte migration, and this may be furthe r dependent on plasmin activation. The results suggest a key role for alpha v beta6 in these processes and indicate a coordinated link between alphav b eta6 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.