GLYCOSAMINOGLYCANS FROM 2 HUMAN-MALIGNANT MESOTHELIOMA CELL-LINES - DETERMINATION, DISTRIBUTION, AND EFFECT OF PLATELET-DERIVED GROWTH-FACTOR ON THEIR SYNTHESIS

The synthesis and distribution of glycosaminoglycans (GAGs) were studi ed in two human malignant mesothelioma cell lines: one with fibroblast -like morphology and the other with epithelial differentiation. Analys es using highly sensitive high-pressure liquid chromatography techniqu es and agarose gel electrophoresis showed that these cells produce not only hyaluronan (HA) but also galactosaminoglycans (GalAGs, chondroit in sulfate and (or) dermatan sulfate) and heparan sulfate (HS). In bot h cell lines most of the HA (87-90%) and GalAGs (57-66%) are secreted into the extracellular matrix. Although HS is mainly bound to the cell surface in fibroblast-differentiated cells (75%), in epithelial type cells only 40% occurs in the cell-associated fraction. The amounts of secreted GAGs are 6- to 8-fold higher in epithelial than in fibroblast -like mesothelioma cultures. In cells with the fibroblast phenotype, t he beta-homodimer of platelet-derived growth factor (PDGF) in a concen tration of 1.5 ng/mL stimulates HA and GalAG synthesis 5-fold and that of HS 10-fold, whereas higher concentrations suppress this stimulator y effect. The stimulatory effect, observed at low concentrations of th is growth factor, was completely blocked by the addition of antibodies against this factor. In epithelially differentiated cells, the produc tion of all GAGs was suppressed after addition of this factor, even at low concentrations. We therefore suggest that mesothelioma cells can produce GAGs, the synthesis of which is dependent on the presence and concentration of PDGF beta-homodimer. The differences between the two cell lines regarding the effect of this growth factor on GAG synthesis indicates that the regulation of this synthesis is complex, other fac tors also being important.