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Basement membrane laminin‐5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for α 3 β 1 integrin
Author(s) -
Lohi Jouni,
Oivula Jan,
Kivilaakso Eero,
Kiviluoto Tuula,
FrÖjdman Kim,
Yamada YOshihiko,
Burgeson Robert E.,
Leivo Ilmo,
Virtanen Ismo
Publication year - 2000
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1034/j.1600-0463.2000.d01-40.x
Subject(s) - basement membrane , laminin , integrin , type iv collagen , pathology , carcinoma , cell adhesion molecule , biology , receptor , chemistry , cancer research , microbiology and biotechnology , extracellular matrix , medicine , biochemistry
Interplay between laminin‐5 (Ln‐5) and its integrin (Int) receptors α 2 β 1 , α 3 β 1 and α 6 β 4 has been implicated in the progression and invasion of carcinomas. In this study we found abundant immuno‐reactivity for chains of Ln‐5 (α3‐β3‐γ2) and Ln‐10 (α5‐β1), 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 α 2 , α 6 , β 1 and β 4 Ints was found in all tumors and that for α 3 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 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 α 3 and β 1 Int subunits, but not those to Int α 2 or α 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 α 3 β 1 Int complex for adhesion to Ln‐5.