Models for angiogenesis in gliomas.

Abstract

During the last decades a lot of attention has been focussed on mechanisms of glioma vascularization, particularly in terms of investigating vascular growth factors and receptors. Recently, these efforts resulted in various approaches for antiangiogenic treatment strategies using in vitro cell culture systems as well as experimental orthotopic and non-orthotopic 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 3-dimensional culture. Recent advances in molecular genetic techniques offer a wide access to the genome of EC. Using these micro array or chip methods differences between micro- and macromolecular EC as well as variations within the gene pool of different organ specific EC can be assessed. 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 weak or non-immunogenic glioma grafts, which 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.