Angiostatin suppresses malignant glioma growth in vivo

摘要: Human malignant gliomas are among the most and intensely vascularized solid tumors. Angiostatin, an internal fragment of plasminogen, was recently discovered as endogenous inhibitor tumor-related angiogenesis by selective inhibition endothelial cell growth. Using xenograft transplants rat primary human glioma cells in immunodeficient mice we investigated effects systemic administration angiostatin purified from plasma on tumor The C6 9L U87 lines implanted either s.c. or intracranially Swiss nude responded to a dose-dependent fashion with growth 11% controls (P < 0.01), without detectable signs toxicity. treated tumors accompanied marked reduction vascularity 38% 0.01) presence up 6-fold increased apoptotic index consistent hypothesis that acts tumoristatic inhibiting tumor-induced proliferation. Expression analysis factors angiostatin-treated revealed 3-fold decrease vascular factor-mRNA 4-fold increase basic fibroblast factor-mRNA, compared untreated 0.01). This suggests tumorigenic phenotype may be mediated part downregulation factor expression within tumor. Our data demonstrate efficiently suppresses vivo. activity against intracranial independent blood brain barrier targeting compartment offer novel therapeutic strategies gliomas.