Overexpression of laminin α1 chain in colonic cancer cells induces an increase in tumor growth

Abstract

Laminins represent a growing family of glycoproteins constituting the basement membrane. They are known to direct many biological processes. With respect to carcinogenesis, laminins play an important role in cell adhesion, mitogenesis, differentiation and even metastasis. To further study the biological significance of laminin- I (composed of α1, β1 and γ1 chains) in intestinal cell differentiation or tumorigenesis, an α1-laminin expression vector was introduced into the HT29 colonic cancer cells, in which laminin α1 chain is not expressed. Upon transfection of the α1 chain, the α1β1γ1 trimer was found secreted in the media along with free α1 chain as assessed by immunoprecipitation. The presence of the laminin α1 chain did not significantly modify the levels of the other laminin chains nor the integrins expressed by the HT29 cells. In spite of similar growth properties with the control cells in vitro (plastic dish, soft agar), the laminin α1 transfectants showed a significantly increased tumor growth when injected in nude mice. Histologic and immunohistochemic examination of the laminin α1-expressing tumors points to an increased recruitment of the host stromal and vascular cells, without modification in the differentiation profile and invasion potential. In parallel, a clear accumulation of laminin-10 (α5β1γ1) at the carcinoma/stromal interface and a segregation of the integrin β4 subunit at the basal pole of the cancer cells occurred, compared to control tumors. Overall, our observations emphasize the importance of laminin-1 as a chemoattractant of both stromal and vascular cells and in epithelial/stromal cell interactions for the organization of the basement membrane and segregation of integrins leading to an epithelial cell growth signal. Such a sequence of events is reminiscent of what occurs during development. © 2001 Wiley-Liss, Inc.