MDA-9/syntenin is a key regulator of glioma pathogenesis

摘要: Background. The extraordinary invasiveness of human glioblastoma multiforme (GBM) contributes to treatment failure and the grim prognosis patients diagnosed with this tumor. Consequently, it is imperative define further cellular mechanisms that control GBM invasion identify promising novel therapeutic targets. Melanoma differentiation associated gene –9 (MDA-9/syntenin) a highly conserved PDZ domain –containing scaffolding protein promotes metastasis in vitro vivo melanoma models. To determine whether MDA-9/syntenin relevant target GBM, we investigated its expression tumor samples involvement angiogenesis. Materials. We assessed levels available databases, patient samples, human-derived cell lines. Through gain-of-function loss-of-function studies, analyzed changes invasion, angiogenesis, signaling vitro. used orthotopic xenografts GBM6 cells demonstrate role pathogenesis vivo. Results. high-grade astrocytomas significantly higher than normal tissue counterparts. Forced overexpression enhanced Matrigel while knockdown inhibited migration, anchorage-independent growth soft agar. Moreover, increased activation c-Src, p38 mitogen-activated kinase, nuclear factor kappa-B, leading elevated matrix metalloproteinase 2 secretion interleukin-8 corresponding observed upon knockdown. stably express small hairpin RNA for formed smaller tumors had less invasive phenotype Conclusions. Our findings indicate important mediator key regulator pathogenesis, as potential anti-invasive astrocytoma.