Invasion as limitation to anti-angiogenic glioma therapy.

摘要: The inhibition of tumor angiogenesis could be an efficient therapeutic strategy for the treatment malignant gliomas. Prominent neovascularization is induced by these tumors, and microvascular proliferation a malignancy grading criterion. However, glioma cells can also invade brain diffusely over long distances without necessarily requiring angiogenesis. Experimentally, it was shown that especially during early stages growth in rodent brain, coopt preexistent host vasculature to recruit their blood supply absence neovascularization. This phenomenon only observed orthotopic models which were implanted into densely vascularized environment, but not subcutaneous are virtual space. Using mouse model, we analyzed whether systemic anti-angiogenic therapy with antibody against vascular endothelial factor receptor-2 (VEGFR2) inhibit intracerebral xenografted human glioblastoma what effect this had on morphology invasiveness. We found inhibited 80% compared buffer-treated controls. intratumoral microvessel density reduced at least 40% treated animals mice anti-VEGFR-2 antibody, noticed striking increase number total area small satellite tumors clustered around primary mass. These satellites usually contained central vessel cores, often migrated along vessels eventually reach surface spread subarachnoid Systemic thus apparently invasiveness gliomas model. Tumor cell invasion tightly associated vessels, suggesting increased cooption represent compansatory mechanism selected inhibiting adequate vascularization.