The overall goal of this research proposal is to investigate the functional significance of vascular endothelial growth factor (VEGF) isoforms during tumor growth and angiogenesis using mouse models. There is growing evidence to support differential functions of VEGF isoforms. My proposed studies will use a spontaneous tumorigenesis model, as well as tumor implant models in which the tumor cells and/or host stromal cells express specific VEGF isoforms. In the spontaneous tumor model, I will determine the function of VEGF isoforms expressed by tumor and stroma cells in the sequence of events leading from normal cells to solid tumors. In the tumor implant models, I will determine the relative contribution of VEGF isoforms expressed in the tumor or the surrounding stromal cells. Finally, potential mechanisms of differential VEGF isoform action will be assessed. ? ? ?
