THE RELATED FLT4, FLT1, AND KDR RECEPTOR TYROSINE KINASES SHOW DISTINCT EXPRESSION PATTERNS IN HUMAN FETAL ENDOTHELIAL-CELLS

The growth factor receptors expressed on endothelial cells are of spec ial interest because of their potential to program endothelial cell gr owth and differentiation during development and neovascularization in various pathological states, such as wound healing and angiogenesis as sociated with tumorigenesis. Vascular endothelial growth factor ([VEGF ] also known as vascular permeability factor) is a potent mitogen and permeability factor, which has been suggested to play a role in embryo nic and tumor angiogenesis. The newly cloned FLT4 receptor tyrosine ki nase gene encodes a protein related to the VEGF receptors FLT1 and KDR /FLK-1. We have here studied the expression of FLT4 and the other two members of this receptor family in human fetal tissues by Northern and in situ hybridization. These results were also compared with the site s of expression of VEGF and the related placenta growth factor (PlGF). Our results reveal FLT4 mRNA expression in vascular endothelial cells in developing vessels of several organs. A comparison of FLT4, FLT1 a nd KDR/FLK-1 receptor mRNA signals shows overlapping, but distinct exp ression patterns in the tissues studied. Certain endothelia lack one o r two of the three receptor mRNAs. These data suggest that the recepto r tyrosine kinases encoded by the FLT gene family may have distinct fu nctions in the regulation of the growth/differentiation of blood vesse ls.