Laminin and collagen IV subunit distribution in normal and neoplastic tissues of colorectum and breast

Abstract

To invade and metastasize, carcinomas must penetrate or lose their epithelial basement membrane (EBM), and then penetrate basement membranes (BMs) surrounding blood vessels, lymphatics, nerves and muscle cells. Knowledge of the composition of different BMs is necessary, so that appropriate antibodies and DNA probes are used to analyse these events. Laminin and type IV collagen are the principal BM components. However, recent studies show these two proteins exist in various isoforms, each of which is a heterotrimer of different subunit polypeptides. In this study, we analysed the distribution of laminin subunits, α1(lam), α2(lam), β1(lam), β2(lam) and γ1(lam), and collagen IV subunits, α1(IV), α3(IV), α4(IV) and α5(IV), in normal and neoplastic tissues of colorectum and breast. Subunits α1(IV), α1(lam), β1(lam) and γ1(lam) were detected in all BMs, while the distribution of α3(IV), α4(IV), α5(IV) and α2(lam) was much more restricted. In carcinomas, EBM staining for all subunits was invariably discontinuous or absent, consistent with the presence of complete EBM breaks. Use of antibody to α1(lam) selectively stained the EBMs of carcinomas. Strong vascular staining for α1(lam), β1(lam), γ1(lam) and α1(IV) suggests an abundance of BM proteins in vessel walls, which may aid tumour cell attachment before vascular invasion. Within carcinomas, vascular BM staining for β2(lam) was clearly weaker than in normal tissues, which may reflect incomplete maturation of these vessels.