Models for assessment of angiogenesis in gliomas

In the last two decades, much attention has been focussed on mechanisms of glioma vascularization including the investigation of growth factors and receptors involved. Recently, these efforts resulted in various approaches for antiangiogenic treatment of experimental brain tumors. These basic science and preclinical trials need an assortment of models, which should allow investigating a variety of questions. Several objectives concerning basic endothelial cell (EC) characteristics can adequately be studied in vitro using EC monolayer assays. Three-dimensional spheroid techniques respect the more complex cell-cell and cell-environment interplay within a three-dimensional culture. To optimize the imitation of the crucial interaction of human gliomas with host endothelial cells, immunological cells and extracellular matrix, animal models are mandatory. An essential rule is to utilize an orthotopic model, since tumor-host interaction is organ specific. To avoid alloimmunogenic responses, it is desirable to use weakly or not immunogenic glioma grafts, what is best accomplished in a syngeneic model. However, since rat gliomas poorly resemble human glioma growth patterns, human glioma xenografting into immunocompromized animals should be considered. In vivo monitoring techniques like videoscopy via a cranial window or magnetic resonance imaging (MRI) allow for functional studies and improve the validity of the model employed. Finally, it is essentially to recognize the limitations of each model considered and to select that model, which seems to be most appropriate for the objectives to be investigated.