Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for α3β1 integrin
Abstract:Interplay between laminin-5 ( Ln-5) and its integrin ( Int) receptors α2β1 , α3β1 and α6β4 has been implicated in the progression and invasion of carcinomas. In this study we found abundant immunoreactivity for chains of Ln-5 (α3-β3-γ2) and Ln-10 (α5-β1-γ1), 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 α1 chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for α2 , α6 , β1 and β4 Ints was found in all tumors and that for α3 Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the γ2 chain of Ln-5 was present as typical Mr 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 α3 and β1 Int subunits, but not those to Int α2 or α6 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 α3β1 Int complex for adhesion to Ln-5.
Document Type: Original Article
Affiliations: 1: Department of Anatomy, Institute of Biomedicine, University of Helsinki; 2: Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland 3: Craniofacial Devel. Biol. Regen. Branch, Bethesda; 4: Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Charlestown, USA 5: Department of Pathology, University of Helsinki, Finland
Publication date: March 1, 2000