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Syndecan-2 and apoptosis in osteosarcoma

ABSTRACT: Syndecan-2 was found to act as a tumor suppressor in osteosarcoma and to mediate the apoptotic response to cytotoxic agents. To determine new mechanisms that control cell survival and apoptosis in osteosarcoma cells, we aim to show target genes that are involved downstream of this proteoglycan during apoptosis induction. We aim to compare the modifications induced by syndecan-2 overexpression in two different human osteosarcoma cell lines using a lentiviral vector coding the human syndecan-2.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19913 | GEO | 2013/09/23

SECONDARY ACCESSION(S): PRJNA122095

REPOSITORIES: GEO

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Project description:We aimed to investigate the function of syndecan-1 in tumor cell adhesion and migration, with special focus on the importance of its distinct protein domains, to better understand the structure-function relationship of syndecan-1 in tumor progression. We utilized two mesenchymal tumor cell lines which were transfected to stably overexpress full-length syndecan-1 or truncated variants: the 78 which lacks the extracellular domain except the DRKE sequence proposed to be essential for oligomerization, the 77 which lacks the whole extracellular domain, and the RMKKK which serves as a nuclear localization signal. Various bioassays for cell adhesion, chemotaxis, random movement and wound healing were studied. Furthermore we performed gene microarray to analyze the global gene expression pattern influenced by syndecan-1. We found that full-length syndecan-1 enhanced cell adhesion in a dose-dependent manner. The truncated constructs only affected adhesion marginally, or not at all. Both full-length syndecan-1 and all its distinct domains inhibited serum-induced cell migration and wound closure. The full-length syndecan-1 and the 78 constructs specifically reduced cell motility/migration in random movement assay. Cell adhesion depends on the extracellular domain and also associates with the DRKE motif. Effects of syndecan-1 on migration are more complex; the pro-adhesive effect of the extracellular domain is one factor hampering migration, but the transmembrane/cytoplasmic portion seems to have additional impact. Gene microarray analysis showed that a number of genes involved in cell adhesion and migration were differentially expressed in syndecan-1 overexpressing cells. Our results demonstrate that syndecan-1 regulates mesenchymal tumor cell adhesion and migration, and different domains have differential effects. Our study provides new inputs into the better understanding of structure-function relationship of this PG in tumor progression. Gene expression profiles (Human Gene 1.0 ST) of malignant mesothelioma cells were studied in syndecan-1 overexpressing cells (N=3) and vector control cells (N=3) .

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Syndecan-2 and apoptosis in osteosarcoma

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