A Quantitative Model of Tumor-induced Angiogenesis in the Nude Mouse

Abstract

Novel animal models allowing for the quantification of tumor-induced angiogenesis and cell migration may offer significant insight into the characterization and multidisciplinary treatment of brain tumors. In this study, we seek to establish such a model in tumor-bearing brain, allowing for a clear demarcation of primary and satellite tumor tissue in conjunction with precise quantification of cerebral microvasculature. We used green fluorescent protein-transfected 9L-gliosarcoma cells stereotactically injected into the brain parenchyma of nude mice perfused with tetramethylrhodamine-dextran immediately before they were killed. New three-dimensional analytical software developed in our laboratory provided a quantitative analysis of laser-scanning confocal microscopy images of dextran-labeled cerebral microvessels. Our data confirm significant angiogenesis in tumor and brain adjacent to tumor. Because these highly infiltrative malignant brain tumors interdigitate with normal brain parenchyma through finger-like projections at the periphery of the solid tumor boundary, therapeutic options targeting tumor blood flow--combined with novel three-dimensional imaging to localize and track such interventions--may offer new hope for glioma management. To our knowledge, this system represents the first animal brain tumor model allowing for the precise colocalization and quantification of angiogenesis and tumor cell invasion, which may play an important role in the development of future therapy for brain tumors.