The outcome of treating primary and metastatic brain tumors with anti-angiogenic therapy in which these agents were delivered in conjunction with chemotherapy and irradiation has been limited to minimal increase in the survival of patients. Paradoxically, in certain mouse tumor models, anti-angiogenic agents injected as single agents, presumably through the inducfion of hypoxia, have enhanced tumor invasiveness. These data have suggested that endothelial cells (ECs) regulate tumor growth not merely by passively delivering oxygen and nutrients. ECs also establish an instructive vascular niche that by production of paracrine growth factors, which we define as
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