VEGF162, A New Heparin-binding Vascular Endothelial Growth Factor Splice Form That Is Expressed in Transformed Human Cells

Abstract

The splice forms of vascular endothelial growth factor (VEGF) differ in biological properties such as the receptor types that they recognize and their interaction with heparan sulfate proteoglycans. We have identified a new VEGF mRNA splice form encoding a VEGF species containing 162 amino acids (VEGF 162 ) in human A431 ovarian carcinoma cells. This novel mRNA contains the peptides encoded by exons 1-5, 6A, 6B, and 8 of the VEGF gene. Recombinant VEGF 162 is biologically active. It induces proliferation of endothelial cells in vitro and angiogenesis in vivo as determined by the alginate bead assay. VEGF 162 binds less efficiently than VEGF 145 but more efficiently than VEGF 165 to a natural basement membrane produced by corneal endothelial cells. VEGF 138 , an artificial VEGF form that contains exon 6B but lacks exons 6A and 7, did not bind to this basement membrane at all, indicating that exon 6B probably interferes with the interaction of exon 6A with heparin and heparan sulfate proteoglycans.

Semaphorin-3F Is an Inhibitor of Tumor Angiogenesis

“…BHK-21 cells transfected with empty expression vector, BHK-21 cells expressing either s3f-l or s3f, or BHK-21 cells expressing VEGF 165 (30) were encapsulated in polylysine-coated microspheres composed of Ca ϩ2 -alginate as described previously (29,31). To evaluate the concentration and viability of the encapsulated cells, capsules containing cells were incubated with 5 mg/ml 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide for 5 h in 37°C, washed three times with 10 mM HEPES (pH 7.3), and incubated for 24 h in isopropanol containing 0.4% HCl at room temperature.…”

“…HUVEC, BHK-21, and porcine aortic endothelial (PAE) cells were cultured as described previously (11,29,30). HUVECs were not used beyond passage 8.…”

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

“…The VEGF gene family currently includes six members: VEGF-A (prototype VEGF), placenta growth factor (PlGF), VEGF-B, VEGF-C, VEGF-D and VEGF-E, (produced by Orf virus), (reviewed by Veikkola et al, 2000). VEGF is a homodimeric glycoprotein that exists in six isoforms containing 121,145,162,165,189 and 206 amino-acid residues as a result of alternative splicing from a single gene (Ferrara and Davis-Smith, 1997;Lange et al, 2003). The predominant and the best characterised VEGF species is the heparin-binding 165-amino acid-long form VEGF 165 (reviewed by Neufeld et al, 1999).…”

“…In the present study, we explored in vitro and in vivo the effects of CMDB7 on human epidermoid carcinoma A431 cells known to produce a high amount of VEGF and a minor quantity of bFGF (Myoken et al, 1991). The other peculiarity of A431 cells is the production of a newly identified splice form of VEGF, VEGF-162, which binds more efficiently than VEGF-165 to a natural basement membrane of endothelial cells (Lange et al, 2003). Moreover, A431 cells express a high level of epidermal growth factor receptors (EGFRs) activated by EGF, a nonheparin-binding growth factor, which does not interact with CMDB7 (Bagheri-Yarmand et al, 1998b).…”

Understanding the Importance of Smart Drugs in Renal Cell Carcinoma

“…By alternative splicing of exons 6 and 7, several transcripts are generated; the produced peptides differ by their ability to bind to heparin and heparan sulfate proteoglycans, forming the extracellular matrix. Until now the 189, 183, 165, 148, 145, 121,162 and 165b VEGF splice forms had been described [33,34] (Fig. 2).…”