The alpha v beta 6 integrin regulates its own expression with cell crowding: Implications for tumour progression

Expression of the growth-promoting integrin alphav betaB in colon cancer ce lls induces gelatinase B secretion and activation, the inhibition of which abolishes alphav beta6-mediated tumour cell growth within a collagen matrix . Herein, we show that high cell density selectively enhances alphav beta6 expression in a protein kinase C (PKC)-dependent manner in preference to ot her beta integrin subunits, resulting in a marked increase in gelatinase B secretion as cells reach confluence. Moreover, PKC activity increases with cell confluence, and the rise in PKC activity is much greater for alphav be ta6-expressing cells than for colon cancer cells which lack alphav beta6. W e propose a self-perpetuating system of colon cancer progression in which t he integrin alphav beta6 provides a means of sustaining tumour cell prolife ration. In this model, alphav beta6 regulates its own expression via a PKC- mediated signalling pathway as tumour cells become crowded and quiescent. T he alphav beta6-mediated induction of gelatinase B secretion facilitates pe ricellular matrix degradation, which helps overcome crowding and restores c ell proliferation, (C) 2001 Wiley-Liss, Inc.