Changes in the expression and distribution of fibronectin, laminin and tenascin by cultured fibroblasts from skin lesions of patients with tuberous sclerosis

Abstract

Fibronectin, laminin and tenascin play an important part in the assembly of the extracellular matrix and the interaction of cells with it. In this study, changes in their expression and distribution associated with tuberous sclerosis are reported. Fibroblasts from three different tuberous sclerosis skin lesions (forehead plaque, neck fibroma and ungual fibroma) secreted more fibronectin and tenascin into their culture medium than did normal skin fibroblasts. Immunohistochemistry and flow cytometry showed that cells from an ungual fibroma which secreted most of each of these glycoproteins also retained more of them, associated mainly with the cell surface and a perinuclear area. Laminin was also produced by all fibroblasts but only in those from the neck fibroma was more both secreted and retained. The proportions of fibronectin/laminin/tenascin secreted by the skin lesion fibroblasts were markedly different from normal. The results suggest that the characteristic tissue hardening of skin lesions in tuberous sclerosis may result, at least in part, from differences in the expression and distribution of these critical components of the extracellular matrix and its consequent abnormal assembly.