Summary Even though many studies suggest that proteoglycans with their structurally determinative polysaccharide chains, the glycosaminoglycans (GAGs), are important mediators of cellular interactions, little is known about expression and possible functions of these macromolecules expressed by tumour cells during the transition from low to highly metastatic behaviour. Therefore, we investigated the cellular expression and secretion of GAGs in a syngeneic tumour system of DBA/2 mice consisting of a methylcholanthrene-induced low metastatic T lymphoma (Eb), its highly metastatic spontaneous variant (ESb), and a low metastatic derivative of ESb (ESb-MP), selected by its adherent growth properties. The [35S]-sulphate-labelled GAGs were isolated from in vitro cultivated cells and further characterized by separation on Sepharose CL 6B, on Mono-Q ion exchange chromatography, and alkali-and enzymatic digestion. In contrast to Eb-cells which produce chondroitin/dermatan sulphate (CS/DS) and heparan sulphate (HS) (cellular extract: CS/DS 67%, HS 33%; culture medium: CS/DS 61%, HS 39%) ESb-and ESb-MP-cells only express and secrete CS/DS. For ESb cells the CS portions consisted of 42% chondroitin-4-sulphate (CS-4) and 58% chondroitin-6-sulphate (CS-6), for ESb-MP cells of 23% CS-4 and 77% CS-6, for Eb cells of 16% CS-4 and 84% CS-6. The cell surface GAGs of the adherent variant ESb-MP contained a significantly higher portion of DS (65%) compared to ESb cells (25%). GAGs of all tumour cell lines studied had a mol. wt ranging from 35-40kD compared to GAG molecular weight standards. Ion exchange chromatography indicated that differences in charge density between GAGs of these cell lines were minimal. These findings suggest that the different biological behaviour of the cell lines cannot be attributed to altered size and charge density of their GAG chains. However, highly metastatic ESb-cells secreted significantly more GAG than low metastatic Eb-and ESb-MP-cells. The possible consequences of the enhanced secretion of CS/DS by ESb-cells are discussed in terms of the postulated role of CS/DS in cellular adhesion, growth regulation and interactions with the immune system. GAGs, the highly anionic sulphated polysaccharide chains of proteoglycans, have been associated with the regulation of cellular interactions, such as cell-cell recognition (Landner et al., 1982), cell-substrate adhesion (Cole et al., 1985;Stamatoglou & Keller, 1983), growth control (Fritze et al., 1985) and masking of cell surface receptors (Fransson et al., 1984). Their ubiquitous expression on the cell surface and in peri-and extracellular spaces suggest that they might play a role in neoplasia and tumour progression (for review see lozzo, 1985). From the data available at the moment it seems that there is not one alteration of proteoglycan expression which is common to all histologically different tumours but rather that each tumour class bears its own characteristic deviations of proteoglycans compared to its normal equivalent.Surprisingly little is known ab...
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