M. Guerrin et al., VASCULOTROPIN VASCULAR ENDOTHELIAL GROWTH-FACTOR IS AN AUTOCRINE GROWTH-FACTOR FOR HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS CULTURED IN-VITRO, Journal of cellular physiology, 164(2), 1995, pp. 385-394
Vasculotropin (VAS), also called vascular endothelial growth factor (V
EGF) or vascular permeability factor, is a secreted growth factor whos
e target cell specificity has been reported as restricted to vascular
endothelium. Its effects are mediated by at least two distinct membran
e-spanning tyrosine kinase receptors, KDR and flt-1, the expression of
which also seems restricted to vascular endothelium. We describe here
that cultured human retinal pigment epithelial (HRPE) cells express b
oth KDR and flt-1 receptors, bind VAS/VEGF on two high affinity sites
(apparent Kd of 9 and 210 pM corresponding to 940 and 18,800 sites per
cell) and proliferate or migrate upon recombinant VAS/VEGF addition.
HRPE cells also express the mRNA corresponding to the 121 and 165 amin
o acid forms of VAS/VEGF. HRPE cells release in their own culture medi
um and store in their extracellular matrix self-mitogenic and chemoatt
ractant factors indistinguishable from 121 and 165 VAS/VEGF isoforms.
The autocrine role of VAS/VEGF was confirmed by the inhibition of thes
e bioactivities by neutralizing specific anti-VAS/VEGF antibodies. (C)
1995 Wiley-Liss, Inc.