Navegando por Palavras-chave "Sindecam"

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    Efeito da resistência à morte celular por perda de adesão (anoikis) na expressão do sindecam-4 e no ciclo celular de células endoteliais em cultura
    (Universidade Federal de São Paulo, 2013-04-25) Carneiro, Bruna Ribeiro [UNIFESP]; Azevedo, Carla Cristina Lopes de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Tumors produce several molecules that facilitate their proliferation, invasion and maintenance, especially proteoglycans. The syndecan-4, a heparan sulfate proteoglycan, can act as a co-receptor of growth factors and proteins of the extracellular matrix (ECM) by increasing the affinity of adhesion molecules to their specific receptors. It participates together with integrins and FAK (focal adhesion kinase) in cell adhesion at focal contacts connecting the ECM to the cytoskeleton. Changes in the expression of syndecan-4 have been found in tumor cells, indicating its involvement in cancer. The acquisition of resistance to cell death induced by blockade of adhesion to the substrate (anoikis resistance) is a feature of neoplastic transformation and a critical step during the metastatic process. Aiming to clarify the role of sindecan-4 in the process of anoikis and in the processes of cell transformation, wild endothelial cells (EC) were subjected to transformation induced by blockade of adhesion to the substrate (Adh-EC) and studied in comparison with endothelial cells transfected with the EJ-ras oncogene (EJ-ras EC) in relation to: tumorigenic capacity, adhesive ability, cell cycle, cell proliferation, synthesis and degradation of sulfated glicosaminoglycans (SGAG), expression and localization of syndecam-4 and heparanase expression. After cycles of blocking adhesion, phenotypic changes were observed in the surviving cells. The clones obtained exhibited characteristics similar to tumorigenic cells: multilayer growth, loss of contact inhibition, tumorigenic capacity, uncontrolled cell cycle, differences at the dependence of growth factors present in fetal bovine serum (FBS), decreased adhesive capacity and a major anti-proliferative effect after treatment with specific inhibitors of PI3K/Akt e Ras/Raf/MAPK/ERK pathways. Further, an increase in the synthesis of heparan sulfate (HS) was detected in the clones resistant to anoikis. This increase is observed for both HS chains present in cells and secreted to culture medium. Structural changes in HS chains were also observed. We have seen that there is an increase in the syndecan-4 and heparanase expression in EJ-ras EC and Adh-EC cells. The data suggests that the syndecan-4 is involved in the acquisition of resistance to cell death induced by blockade of adhesion to the substrate (resistance to anoikis), contributing to neoplastic transformation.