Differentiation of mesothelioma cells is influenced by the expression of proteoglycans

Malignant mesothelioma characteristically shows epithelial and/or sarcomato us morphology, this phenotypic differentiation being correlated to the prog nosis. The present study was undertaken to see whether proteoglycan (PG) ex pression influences mesothelioma differentiation. To assess this hypothesis , me studied a mesothelioma model, where the cells were induced to differen tiate into epithelial or fibroblastlike morphology, mimicking the biphasic growth of this sarcoma, Series of PGs were analyzed in parallel by semiquan titative reversed transcriptase polymerase chain reaction, showing increase d expression of syndecan-2, syndecan-4, and hyaluronan synthase in the epit helial phenotype, whereas the fibroblast-like cells expressed more matrix P Gs: versican, decorin, and biglycan. Western blotting confirms these differ ences and provides evidence of extensive shedding and rapid turnover of cel l membrane PGs, Experimental down-regulation of the studied syndecans by an tisense targeting resulted in a change in shape from polygonal to spindle-l ike morphology, while syndecan-1 and -4, but not syndecan-2, could be assoc iated with cell aggregation, indicating distinct functions of different syn decans, The PG profile is thus closely associated with the morphology and b iological behavior of tumor cells, mesotheliomas showing a different profil e than true epithelial tumors. (C) 2000 Academic Press.