Overexpression of laminin alpha 1 chain in colonic cancer cells induces anincrease in tumor growth

Laminins represent a growing family of glycoproteins constituting the basem ent membrane. They are known to direct many biological processes. With resp ect to carcinogenesis, laminins play an important role in cell adhesion, mi togenesis, differentiation and even metastasis. To further study the biolog ical significance of laminin-1 (composed of alpha1, beta1 and gamma1 chains ) in intestinal cell differentiation or tumorigenesis, an alpha1-laminin ex pression vector was introduced into the HT29 colonic cancer cells, in which laminin alpha1 chain is not expressed. Upon transfection of the al chain, the alpha1 beta1 gamma1 trimer was found secreted in the media along with f ree alpha1 chain as assessed by immunoprecipitation. The presence of the la minin alpha1 chain did not significantly modify the levels of the other lam inin chains nor the integrins expressed by the HT29 cells. In spite of simi lar growth properties with the control cells in vitro (plastic dish, soft a gar), the laminin alpha1 transfectants showed a significantly increased tum or growth when injected in nude mice. Histologic and immunohistochemic exam ination of the laminin alpha1-expressing tumors points to an increased recr uitment of the host stromal and vascular cells, without modification in the differentiation profile and invasion potential. In parallel, a clear accum ulation of laminin-10 (alpha5 beta1 gamma1) at the carcinoma/stromal interf ace and a segregation of the integrin beta4 subunit at the basal pole of th e cancer cells occurred, compared to control tumors. Overall, our observati ons emphasize the importance of laminin-1 as a chemoattractant of both stro mal and vascular cells and in epithelia/stromal cell interactions for the o rganization of the basement membrane and segregation of integrins leading t o an epithelial cell growth signal. Such a sequence of events is reminiscen t of what occurs during development. (C) 2001 Wiley-Liss, Inc.