The goal of this project is to continue the development of a center at the University of Alabama (UAB) for brain tumor research which was started in 1992 with the awarding of a Brain Tumor Program Project Feasibility Grant. In this resubmission, the emphasis remains on studies of the cellular and molecular biology of malignant glial tumors. The revised Program consists of three laboratory-based Projects and an Administrative Core, which will handle the management of the program and facilitate interactions among group members. Project #1 (Dr. Etty N. Benveniste, Project Leader) will investigate the effects of several glioma-active cytokines on the expression of intercellular adhesion molecule-1 (ICAM1). Studies will focus on the role of the cytokine TGFbeta in suppressing ICAM-1 expression by gliomas, an effect which may allow these tumors to escape immune surveillance. Project #2 (Dr. Candece L. Gladson, Project Leader) will investigate the effects of platelet- derived growth factor (PDGF) on the expression and activity of glioma- derived, vitronectin-binding integrins. Studies will focus on the effects of PDGF on vitronectin-binding, internalization, and degradation, and on structure/function relationships of glioma-expressed integrins. Project #3 (Dr. Steven S. Rosenfeld,Project Leader) will investigate the role of myosin II in glioma invasiveness and angiogenesis. Biophysical and pharmacologic studies will be utilized to design methods of specifically interfering with myosin Ii function. These studies will give a clearer understanding of how myosin II function is regulated and will define parameters that may eventually be utilized in designing new, anti- invasive and anti-angiogenesis therapies. Collaborative interactions between each of the investigators, which were initiated by the awarding of P20 NS 31096, will continue in this Program Project. Taken together, these projects should lead to a better understanding of the cell biology of malignant glial tumors.
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