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Differentiation of Mesothelioma Cells Is Influenced by the Expression of Proteoglycans

Authors
Journal
Experimental Cell Research
0014-4827
Publisher
Elsevier
Publication Date
Volume
258
Issue
1
Identifiers
DOI: 10.1006/excr.2000.4915
Keywords
  • Mesothelioma
  • Proteoglycans
  • Syndecan
  • Differentiation
  • Cell–Cell Interactions
  • Cell–Matrix Interactions
Disciplines
  • Biology

Abstract

Abstract Malignant mesothelioma characteristically shows epithelial and/or sarcomatous morphology, this phenotypic differentiation being correlated to the prognosis. The present study was undertaken to see whether proteoglycan (PG) expression influences mesothelioma differentiation. To assess this hypothesis, we studied a mesothelioma model, where the cells were induced to differentiate into epithelial or fibroblast-like morphology, mimicking the biphasic growth of this sarcoma. Series of PGs were analyzed in parallel by semiquantitative reversed transcriptase polymerase chain reaction, showing increased expression of syndecan-2, syndecan-4, and hyaluronan synthase in the epithelial phenotype, whereas the fibroblast-like cells expressed more matrix PGs: versican, decorin, and biglycan. Western blotting confirms these differences and provides evidence of extensive shedding and rapid turnover of cell membrane PGs. Experimental down-regulation of the studied syndecans by antisense targeting resulted in a change in shape from polygonal to spindle-like morphology, while syndecan-1 and -4, but not syndecan-2, could be associated with cell aggregation, indicating distinct functions of different syndecans. The PG profile is thus closely associated with the morphology and biological behavior of tumor cells, mesotheliomas showing a different profile than true epithelial tumors.

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