Transforming growth factor beta1 (
TGFbeta) simultaneously induces the expression of
fibronectin,
fibronectin receptor,
laminin, and
laminin receptor (
alpha6beta1 integrin) in the human
colon cancer cell line Moser (Int J
Cancer, 57:742, 1994). Induction of
fibronectin and induction of
fibronectin receptor by TGFB are tightly coupled, and disrupting
fibronectin induction disrupts the induction of
fibronectin receptor and cellular adhesion to
fibronectin (J Cellular Physiol, 170:138, 1997). We recently demonstrated the efficacy of using antisense chain-specific
laminin RNA expression vectors to disrupt the induction by TGFP of the multichain
laminin molecule (J Cellular Physiol, 178:296, 1999). We now show in this report that Moser cells used alpha6 and beta1
integrins to adhere to
laminin, and, as is the
fibronectin and
fibronectin receptor system, disrupting the induction by
TGFbeta of the
ligand laminin by the expression of antisense
laminin A chain
RNA disrupted the induction of 125I-laminin binding and cellular adhesion to
laminin. Disrupting
laminin induction also blocked the induction of alpha6 and
beta1 integrin laminin receptor by
TGFbeta. We conclude that disrupting the induction of the
ligand laminin by
TGFbeta disrupts
TGFbeta-regulated
laminin receptor function by suppressing the induction of alpha6 and beta1
integrins. Therefore, targeted disruption of the
ligand laminin may be an effective means in disrupting the function of both the
ligand and its receptor in cells that utilize the
laminin and
laminin receptor system in malignant cell behavior.