TUMOR-INDUCTION OF VEGF PROMOTER ACTIVITY IN STROMAL CELLS

We have established a line of transgenic mice expressing the A. victor ia green fluorescent protein (GFP) under the control of the promoter f or vascular endothelial growth factor (VEGF). Mice bearing the transge ne show green cellular fluorescence around the healing margins and thr oughout the granulation tissue of superficial ulcerative wounds. Impla ntation of solid tumors in the transgenic mice leads to an accumulatio n of green fluorescence resulting from tumor induction of host VEGF pr omoter activity. With time, the fluorescent cells invade the tumor and can be seen throughout the tumor mass. Spontaneous mammary tumors ind uced by oncogene expression in the VEGF-GFP mouse show strong stromal, but not tumor, expression of GFP. In both wound and tumor models the predominant GFP-positive cells are fibroblasts. The finding that the V EGF promoter of nontransformed cells is strongly activated by the tumo r microenvironment points to a need to analyze and understand stromal cell collaboration in tumor angiogenesis.