EFFECT OF INSULIN AND EPIDERMAL GROWTH-FACTORS ON THE SYNTHESIS OF GLYCOSAMINOGLYCANS PROTEOGLYCANS IN CULTURED HUMAN-MALIGNANT MESOTHELIOMA CELLS OF DIFFERENT PHENOTYPIC MORPHOLOGY/

Two human malignant mesothelioma cell sublines, one with a fibroblast- like and the other with an epithelial differentiation, were examined f or their capacity to synthesize glycosaminoglycans in the presence of IGF-I, EGF, and their combination. This synthesis depends on the morph ology of the mesothelioma cells, with many-fold higher amounts of both hyaluronan and proteoglycans being produced by the cells with epithel ial morphology than by those of the fibroblast phenotype. In both cell lines this synthesis was affected in a dose-dependent fashion by the exogenously added growth factors and exposure to IGF-I and EGF in comb ination showed a synergistic effect. This effect of those factors seem s to be mediated via protein tyrosin kinase-dependent receptors and wa s different in the fibroblast-like and epithelial cells. The synthetic rates of the various glycosaminoglycans formed (hyaluronan, galactosa minoglycans and heparan sulfate) were also variously affected by these factors, indicating differences in how the synthesis of the various g lycosaminoglycans is regulated. The results obtained suggest a close c orrelation between the presence of the appropriate growth factor(s), t he process of cell differentiation and the synthesis of glycosaminogly cans in these cells.