Análise de glicosaminoglicanos e proteoglicanos em linhagens tumorais de próstata / Analysis of glycosaminoglycans and proteoglycans in prostate cancer cell lines

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Proteoglycans (PG) are cell surface, extracellular matrix and citoplasmatic granule macromolecules, that play an important role in cellcell and cell-matrix interactions. Several studies indicated that significant changes in PG content occur in the tumor stroma of epithelial neoplasms and that these alterations influence tumor growth and invasion. In this study, prostate cancer cell lines DU145 and PC3, from different metastatic origin, brain and bone, respectively, were analyzed for a comparative study of GAGs and PGs. Labeling cells with [35S] Na2SO4 and structural analysis of GAGs with specific enzymes, showed the presence of 6-O-sulfation products on heparan sulfate (HS) and chondroitin sulfate (CS) of PC3 cells compared to DU145 cells. HS products from PC3 cells were represented by increased N-acetylated-6-Osulfated disaccharides (DGlcA-GlcNAc,6OS) and trisulfated disaccharide (DIdoA,2S-GlcNS,6S). 6 and 4-O-sulfation products (DU-GalNAc4S,6S) were also present on CS of PC3 cells, but less on DU 145 cells. Studies in the literature have demonstrated the presence of Ido,A,2S to be an absolute requirement for the ability of HS to bind bFGF. However, studies have shown the need for an additional requirement for 6-O-sulfation of Nsulfated glucosamine residues, for the promotion of the growth factors mitogenic activity. Higher PGHS levels were found on boths cells, compared to PGCS. Syndecan-1 is decreased in PC3 cells in relation to DU145 cells. Moreover, a counterbalance of syndecan-2 increase was detected by real time PCR, and corroborated by confocal microscopy and double labeled flow cytometry. The presence of syndecan-2 in PC3 cells and the changes in its subcellular distribution compared to DU145 cells may represent an important role in prostatic carcinogenesis. Regarding migration studies, DU145 cells showed a more migratory profile, maybe due to the extravasation selective advantage acquired by these cells to overcome the haematoencephalic blood-brain barrier. Collectively, these results demonstrate different biochemical and cellular features between the two lineages, reflecting peculiar aspects of organ-specific colonization and cells-selection acquired during metastasis process.

ASSUNTO(S)

glicosaminoglicanos proteoglicanos cancer de prostata linhagens celulares de câncer de próstata biologia molecular

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