VEGF(145), A SECRETED VASCULAR ENDOTHELIAL GROWTH-FACTOR ISOFORM THATBINDS TO EXTRACELLULAR-MATRIX

A vascular endothelial growth factor (VEGF) mRNA species containing ex ons 1-6 and 8 of the VEGF gene was found to be expressed as a major VE GF mRNA form in several cell lines derived from carcinomas of the fema le reproductive system, This mRNA is predicted to encode a VEGF form o f 145 amino acids (VEGF(145)), Recombinant VEGF(145) induced the proli feration of vascular endothelial cells and promoted angiogenesis in vi vo. VEGF(145) was compared with previously characterized VEGF species with respect to interaction with heparin-like molecules, cellular dist ribution, VEGF receptor recognition, and extracellular matrix (ECM) bi nding ability. VEGF(145) shares with VEGF(165) the ability to bind to the KDR/flk-1 receptor of endothelial cells, It also binds to heparin with an affinity similar to that of VEGF(165). However, VEGF(145) does not bind to two additional endothelial cell surface receptors that ar e recognized by VEGF(165) but not by VEGF(121). VEGF(145) is secreted from producing cells as are VEGF(121) and VEGF(165). However, VEGF(121 ) and VEGF(165) do not bind to the ECM produced by corneal endothelial cells, whereas VEGF(145) binds efficiently to this ECM, Basic fibrobl ast growth factor (bFGF)-depleted ECM containing bound VEGF(145) induc es proliferation of endothelial cells, indicating that the bound VEGF( 145) is active, The mechanism by which VEGF(145) binds to the ECM diff ers from that of bFGF, 145 Digestion of the ECM by heparinase inhibite d the binding of bFGF to the ECM and released prebound bFGF, whereas t he binding of VEGF(145) was not affected by heparinase digestion. It t herefore seems that VEGF(145) possesses a unique combination of biolog ical properties distinct from those of previously characterized VEGF s pecies.