This review deals with
biological and pathological aspects of various
isoforms of the matrix molecules
fibronectin and
laminin. They are generated by different molecular mechanisms: ED-A+ and ED-B+
fibronectin by alternative splicing of
pre mRNA, de novo-
glycosylated fibronectin by alternative post-translational O-linked glycosylation of the IIICS region, and the
laminin isoforms by exchange of single chains of the heterotrimeric molecule. In contrast to the "common"
fibronectin, the distribution of ED-B+ and de novo-
glycosylated fibronectin is restricted to embryonic tissues; they subsequently reappear in granulation tissue, in fibrosing processes and in tumour stroma. The expression of these so-called oncofetal
fibronectins is stimulated by
growth factors (
TGF beta). The association of the ED-B+
fibronectin with proliferative activity and newly formed vessels identifies this
fibronectin variant as a marker of cellular activity in the process of
fibrosis and as a suitable agent for the evaluation of tumour angioneogenesis. Initial results suggest a correlation between the amount of ED-B+ and de novo-
glycosylated fibronectin in tumour stroma and the behaviour of
carcinomas with regard to their invasiveness and propensity for metastatic dissemination. The current nomenclature of the
laminin molecule family is presented. The
laminin chain constitution of basement membranes switches from embryonic or proliferatively active to adult terminally differentiated tissues [disappearance of the
laminin beta 2 (s) chain] and depends on the tissue type. The discrepancy between the loss of basement membranes (multiple basement membrane defects) in
carcinomas and the recently reported increased
laminin chain synthesis in these tumours may be explained by abundant
laminin chain deposition outside the basement membrane in the
carcinoma invasion front, possibly associated with enhanced adhesion of budding tumour cells.