Expression of the integrin α6β4, a receptor for the laminin family of matrix proteins, has been correlated with the progression and metastatic potential of several different tumors, including colorectal carcinoma. For this reason, defining the mechanistic contribution of α6β4 to the aggressive behavior of colorectal and other carcinoma cells is an issue of timely importance for cancer biology. In the present study, we sought to gain insight into the function of α6β4 in colorectal carcinoma cells by studying the behavior of clone A cells, which express high surface levels of this integrin, and by restoring α6β4 expression in RKO cells, a β4- deficient rectal carcinoma cell line. The data obtained reveal that α6β4 expression increases the adhesive strength of these cells on laminin-1 matrices, although it does not increase their ability to migrate on such matrices. The RKO/β4 transfectants were considerably more spread on Matrigel, laminin-1, and collagen I than the mock transfectants and displayed numerous extensions suggestive of pseudopodia. More importantly, we discovered that expression of α6β4 facilitates the ability of colorectal carcinoma cells to invade both Matrigel and collagen I matrices. The α6β4-dependent increases in adhesion and invasion, as well as the observed morphological changes, required an intact β4 cytoplasmic domain. These data argue for a ligand-independent role for α6β4 in promoting cell invasion, and they have important implications for the involvement of this integrin in colorectal carcinoma progression.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Oct 15 1996|