Tumor cell attachment to laminin promotes degradation of the extracellular matrix and cell migration in high-metastatic clone cells of RCT sarcoma in vitro.

We investigated the roles of extracellular matrix proteins, laminin and fibronectin, in promoting invasiveness through the extracellular matrix in high-metastatic [RCT(+)] clone cells established from poorly differentiated murine RCT sarcoma in C3H/He mice. Laminin stimulated the type IV collagenolytic activity of RCT(+) cells. After more than 6 h of incubation, the type IV collagenolysis of the cell-conditioned medium was significantly higher in laminin-treated groups compared with the control. The migration activity of RCT(+) cells was stimulated by laminin. However, fibronectin did not influence the type IV collagenolysis or cell migration in this clone cell. The amino acid sequence YIGSR, which is derived from laminin, inhibited the laminin-mediated cell attachment and the laminin-promoted type IV collagenolysis, as well as cell migration of RCT(+) cells. RGD derived from fibronectin did not influence the cell attachment to laminin or Matrigel in this clone. In the invasion assay employing a Matrigel coated filter in a Boyden chamber, YIGSR showed greater inhibition of invasion through the Matrigel than did RGD with RCT(+) cells. YIGSR might inhibit the promoted-matrix degradation and cell migration in response to the cell attachment to laminin by competing with laminin for binding to cell surface laminin receptor. We suggest that laminin-mediated cell attachment to the extracellular matrix may play a role in promoting the matrix degradation and cell migration during metastatic cascades.