Differential expression of laminin-5 subunits and integrin receptors in human colorectal neoplasia

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Abstract
Cell‐matrix interactions contribute to regulating the adhesion, growth, migration, and differentiation of epithelial intestinal cells. Alterations in matrix components and their cellular receptors have been found in tumours but their specific roles remain unclear. The tissue patterns of laminin‐5 and α3, β3 and γ2 subunits, as well as those of the α3, α6, β1, and β4 integrin chains, were determined by immunofluorescence on frozen sections of 12 colorectal mucosal samples from four patients, 15 adenomas, 29 adenocarcinomas, and eight metastases. Distinct patterns of laminin‐5 and integrin expression were found along the mucosa–adenoma and adenoma–carcinoma transitions. Expression of basement membrane laminin‐5 and subunits was continuous and gradient‐like in normal mucosa, enhanced at the periphery of adenomas, and discontinuous in places in carcinomas and metastases. Decrease of the α3 integrin chain was found in adenomas, together with that of α6 and β4 chains in carcinomas. A subpopulation of carcinoma cells dissociating (budding) from neoplastic tubules was found to accumulate the laminin‐5 β3γ2 heterodimer in the cytoplasm, with progressive loss of surface integrin expression. These results suggest that in colorectal cancer, an abnormal expression of laminin‐5 subunits and integrin chains may identify a subset of carcinoma cells prone to invade focally and to contribute to disease aggressiveness. © 1998 John Wiley & Sons, Ltd.