UTERINE SMOOTH-MUSCLE CELLS EXPRESS FUNCTIONAL RECEPTORS (FLT-1 AND KDR) FOR VASCULAR-PERMEABILITY FACTOR VASCULAR ENDOTHELIAL GROWTH-FACTOR/

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is an angiogenic factor with important roles in tumor growth, wound healing, and inflammation. VPF/VEGF interacts wit h endothelial cells by way of two high-affinity receptor tyrosine kina ses: fit-1 and KDR. The vast majority of published studies have descri bed expression of the VPF/VEGF receptors only in endothelial cells, an d the statement is frequently made that these receptors are endothelia l-cell-specific. In this study, we detected mRNA for fit-1 and KDR by in situ hybridization in smooth muscle cells in sections of the wall o f the uterus. To confirm these unexpected findings, smooth muscle cell s from the uterus and, as a control, from the colon were isolated, cha racterized, and cultured. Both uterine and colonic smooth muscle cells in culture expressed VPF/VEGF, but only smooth muscle cells from the uterus expressed mRNA for fit-1 and KDR by Northern analysis and in si tu hybridization. Cell culture extracts of uterine but not colonic smo oth muscle cells were also positive for fit-1 by Western analysis. Mor eover, cultured uterine but not colonic smooth muscle cells phosphoryl ated the fit-1 receptor and proliferated strongly in response to added VPF/VEGF. This is one of the first rigorous demonstrations that a nor mal cell type other than endothelial cells can express functional rece ptors for VPF/VEGF in vivo and in vitro, suggesting that VPF/VEGF may have important, previously unsuspected roles on cell types other than endothelium.