Differentiation of mesothelioma cells is influenced by the expression of proteoglycans.
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.
Department of IMPI, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
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K
Dobra
M
M
Andäng
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A
Syrokou
N K
NK
Karamanos
A
A
Hjerpe
D058578:Biglycan; D002454:Cell Differentiation; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D058575:Decorin; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics; D016695:Glycosyltransferases; D006801:Humans; D000076002:Hyaluronan Synthases; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011509:Proteoglycans / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053669:Syndecan-2; D053671:Syndecan-4; D014166:Transferases; D014407:Tumor Cells, Cultured; D053675:Versicans; D029867:Xenopus Proteins
C546884:BGN protein, human; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011509:Proteoglycans; C508245:SDC2 protein, human; C508304:SDC4 protein, human; D053671:Syndecan-4; C508322:VCAN protein, human; D029867:Xenopus Proteins; C508248:sdc2 protein, Xenopus; D053675:Versicans; D053669:Syndecan-2; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases