Preferential expression of functional IL-17R in glioma stem cells: potential role in self-renewal
作者： Prahlad Parajuli , Rohit Anand , Chandramouli Mandalaparty , Raviteja Suryadevara , Preethi U. Sriranga
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摘要: Gliomas are the most common primary brain tumor and one of lethal solid tumors. Mechanistic studies into identification novel biomarkers needed to develop new therapeutic strategies for this deadly disease. The objective study was explore potential direct impact IL-17-IL-17R interaction in gliomas. Immunohistochemistry flow cytometry analysis 12 samples obtained from patients with high grade gliomas revealed that a considerable population (2-19%) cells all malignant expressed IL-17RA, remarkable co-expression glioma stem cell (GSC) markers CD133, Nestin, Sox2. IL-17 enhanced self-renewal GSCs as determined by proliferation Matrigel® colony assays. also induced cytokine/chemokine (IL-6, IL-8, interferon-γ-inducible protein [IP-10], monocyte chemoattractant protein-1 [MCP-1]) secretion GSCs, which were differentially blocked antibodies against IL-17R IL-6R. Western blot showed modulated activity signal transducer activator transcription 3 (STAT3), nuclear factor κ-light-chain-enhancer activated B (NF-κB), glycogen synthase kinase-3β (GSK-3β) β-catenin GSCs. While IL-17R-mediated IL-6 IL-8 significantly inhibitors NF-κB STAT3; inhibitor more potent than STAT3 blocking IL-17-induced MCP-1 secretion. Overall, our results suggest induces an autocrine/paracrine cytokine feedback loop, may provide important signaling component maintenance/self-renewal via constitutive activation both STAT3. strongly implicate functional biomarker targeting
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