Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for alpha(3)beta(1) integrin

Interplay between laminin-5 (Ln-5) and its integrin (Int) receptors alpha(2)beta(1), alpha(3)beta(1) and alpha(6)beta(4) has been implicated in the progression and invasion of carcinomas. In this study we found abundant immunoreactivity for chains of Ln-5 (alpha 3-beta 3-gamma 2) and Ln-10 (alpha 5-beta 1-gamma 1), as well as for type VII collagen, in basement membranes (BM) of colorectal adenomas. In carcinomas of all differentiation grades, Lns were seen in tumor BMs, whereas type VII collagen was almost absent. Ln-5 appeared to accumulate along the invading edges of carcinomas, while Ln-10 was mostly absent. Immunoreactivity for Ln al chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for alpha(2), alpha(6), beta(1) and beta(4) Ints was found in all tumors and that for alpha(3) Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the gamma 2 chain of Ln-5 was present as typical M-r 105000 and 155000 isoforms. Immunoprecipitation experiments showed production of Ln-5 by cultured colon carcinoma cells. In quantitative cell adhesion experiments, function-blocking MAbs to alpha(3) and beta(1) Int subunits, but not those to Int alpha(2) or alpha 6 subunits, significantly inhibited the adhesion of cells to Ln-5. Our results suggest that BM composition in colorectal adenomas reflects the properties of surface epithelial BM of colorectal mucosa. In invading carcinomas, trimeric Ln-5, produced by carcinoma cells, is a major BM component and the cells use the alpha(3)beta(1) Int complex for adhesion to Ln-5.