The basic residues of placenta growth factor type 2 retrieve sequestered angiogenic factors into a soluble form: implications for tumor angiogenesis.
Placenta growth factor type 1 (PIGF-1) can be synthesized by neoplastic cells in an alternative form (PIGF-2) by the addition of basic amino acids to its classic sequence. Here we show that the basic residues of PIGF-2 compete for the binding of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) to heparan sulfate proteoglycans of the cell surface and extracellular matrix. In doing so, PIGF-2 basic sequences inhibit the sequestering of VEGF and bFGF and maintain them in a highly diffusible form, thus enhancing their angiogenic effect. In agreement with these in vitro data, the presence of PIGF-2 transcripts in tumors correlates with their blood vessel number. These results suggest a mechanism by which growth factor isoforms produced by neoplastic cells enhance the formation of new blood vessels supporting tumor growth and progression.
Barillari
G
G
Department of Experimental Medicine, University Tor Vergata, Rome, Italy.
Albonici
L
L
Franzese
O
O
Modesti
A
A
Liberati
F
F
Barillari
P
P
Ensoli
B
B
Manzari
V
V
Santeusanio
G
G
D043925:Angiogenesis Inducing Agents / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D000072483:Placenta Growth Factor; D016133:Polymerase Chain Reaction; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D006133:Growth Substances; D019812:Heparan Sulfate Proteoglycans; D008222:Lymphokines; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor