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PMID: 9588884 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The basic residues of placenta growth factor type 2 retrieve sequestered angiogenic factors into a soluble form: implications for tumor angiogenesis.

The American journal of pathology ·Vol. 152 ·No. 5 ·1998-05-00 ·Pages 1161-6

Barillari G, Albonici L, Franzese O, Modesti A, Liberati F, Barillari P, Ensoli B, Manzari V, Santeusanio G

Abstract

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.

MeSH Terms
Angiogenesis Inducing Agents/genetics,metabolism,pharmacology Endothelial Growth Factors/metabolism Endothelium, Vascular/drug effects,metabolism Extracellular Matrix/metabolism Fibroblast Growth Factor 2/metabolism Growth Substances/genetics,metabolism,pharmacology Heparan Sulfate Proteoglycans/metabolism Humans Immunoenzyme Techniques Lymphokines/metabolism Neoplasms/blood supply,metabolism,pathology Neovascularization, Pathologic/metabolism,pathology Placenta Growth Factor Polymerase Chain Reaction Pregnancy Proteins/genetics,metabolism,pharmacology RNA, Messenger/metabolism Tumor Cells, Cultured Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Angiogenesis Inducing Agents Endothelial Growth Factors Growth Substances Heparan Sulfate Proteoglycans Lymphokines PGF protein, human Pregnancy Proteins RNA, Messenger Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Fibroblast Growth Factor 2 Placenta Growth Factor
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Barillari G
Department of Experimental Medicine, University Tor Vergata, Rome, Italy.
Albonici L
Franzese O
Modesti A
Liberati F
Barillari P
Ensoli B
Manzari V
Santeusanio G
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1998-05-00
Pages
1161-6
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1858577
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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