Distribution of laminin and fibronectin isoforms in oral mucosa and oral squamous cell carcinoma

The expression of laminin and fibronectin isoforms varies with cellular mat uration and differentiation and these differences may well influence cellul ar processes such as adhesion and motility. The basement membrane (BM) of f etal oral squamous epithelium contains the laminin chains, alpha 2, alpha 3 , alpha 5, beta 1, beta 2, beta 3, gamma 1 and gamma 2. The BM of adult nor mal oral squamous epithelium comprises the laminin chains, alpha 3, alpha 5 , beta 1, beta 3, gamma 1 and beta 2. A re-expression of the laminin alpha 2 and beta 2 chains could be shown in adult hyperproliferative, dysplastic and carcinomatous lesions. In dysplasia and oral squamous cell carcinoma (O SCC), multifocal breaks of the BM are present as indicated by laminin chain antibodies. These breaks correlate to malignancy grade in their extent. Mo reover, in the invasion front the alpha 3 and gamma 2 chain of laminin-5 ca n immunohistochemically be found outside the BM within the cytoplasm of bud ding carcinoma cells and in the adjacent stroma. The correlation between th e morphological pattern of invasive tumour clusters and a laminin-5 immunos taining in the adjacent stroma may suggest, first, that a laminin-5 deposit ion outside the BM is an immunohistochemical marker for invasion and second , that OSCC invasion is guided by the laminin-5 matrix. Expression of oncof etal fibronectins (IIICS de novo glycosylated fibronectin and ED-B fibronec tin) could be demonstrated throughout the stromal compartment. However, the ED-B fibronectin synthesizing cells (RNA/RNA in situ hybridization) are co nfined to small stroma areas and to single stroma and inflammatory cells in the invasion front, A correlation of the number of ED-B fibronectin synthe sizing cells to malignancy grade could not be seen. ED-B fibronectin mRNA-p ositive cells seem to be concentrated in areas of fibrous stroma recruitmen t with a linear alignment of stromal fibro-/myofibroblasts (desmoplasia). D ouble staining experiments (ED-B fibronectin in situ hybridization and alph a-smooth muscle actin immunohistochemistry) indicated that the stroma myofi broblasts are a preferential source of ED-B fibronectin. In conclusion, in OSCC, a fetal extracellular matrix conversion is demonstrable. Tumour cells (laminin alpha 2 and beta 2 chain) and recruited stromal myofibroblasts (o ncofetal ED-B fibronectin) contribute to the fetal extracellular matrix mil ieu. (C) 1999 Cancer Research Campaign.