Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo.

摘要: Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported multiple types cancer including glioblastoma (GBM), the highest grade aggressive brain tumor. GBMs contain subpopulation glioma-initiating cells (GICs) implicated progression, therapeutic resistance recurrence. We have previously demonstrated that silencing inhibited GBM cell growth vitro vivo. Moreover, activation CD44 signaling upon ligation recently acquisition stem phenotype by cells. The present study aimed to explore autocrine function using shRNA strategy GICs enriched from lines human primary grown EGF bFGF defined medium. removal these factors addition serum induced significant loss GICs. showed OPN-silenced were unable grow as spheres this capacity was restored exogenous OPN. Importantly, Sox2, Oct3/4 Nanog, key stemness transcription factors, significantly decreased targeting. identified Akt/mTOR/p70S6K main pathway triggered following OPN-mediated EGFR Finally, an orthotopic xenograft mouse model, tumorigenic potential U87-MG sphere completely abrogated silencing. Our demonstration endogenous major regulatory effects on tumorigenicity implies greater role than anticipated for pathogenesis initiation probable