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PMID: 7514607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PDGF-BB modulates endothelial proliferation and angiogenesis in vitro via PDGF beta-receptors.

The Journal of cell biology ·Vol. 125 ·No. 4 ·1994-05-00 ·Pages 917-28

Battegay EJ, Rupp J, Iruela-Arispe L, Sage EH, Pech M

Abstract

To delineate potential angiogenic roles of platelet-derived growth factor (PDGF), we have investigated PDGF and its receptors on bovine aortic endothelial cells that exhibit spontaneous angiogenesis in vitro (angiogenic endothelial cells). Initiation of cord/tube formation by angiogenic endothelial cells required bovine or human serum. Neutralization of PDGF-BB in human serum with a monoclonal anti-PDGF-BB antibody reduced cord/tube formation by 37 +/- 10%, whereas neutralizing anti-PDGF-AA and an IgG isotype-matched control antibody had no effect. DNA synthesis in response to PDGF-BB increased as the cords and tubes developed; furthermore, PDGF-BB induced the incorporation of BrdU in the nuclei of cells associated with these structures. PDGF beta-receptor (PDGF-beta) mRNA increased concomitantly with cord/tube formation, and PDGFR-beta were specifically localized by immunocytochemistry to developing and mature cords and tubes. However, PDGFR-beta transcripts and protein were undetectable in nonangiogenic endothelial cells, and PDGF alpha-receptor mRNA was not expressed in either endothelial cell strain. In contrast to nonangiogenic endothelial cells, angiogenic endothelial cells did not express the PDGF B-chain, the required ligand for the PDGFR-beta. We conclude that (a) PDGF-BB can contribute to angiogenesis in vitro, (b) PDGFR-beta are specific for cord/tube-forming endothelial cells and mediate endothelial proliferation and cord/tube formation, and (c) in angiogenic and nonangiogenic endothelial cells, the expression of PDGFR-beta and PDGF B-chain is inversely correlated. We therefore suggest that paracrine PDGF might amplify angiogenesis via direct action on endothelially expressed PDGFR-beta.

MeSH Terms
Animals Becaplermin Cattle Cell Division Cells, Cultured Culture Media Culture Media, Serum-Free DNA/biosynthesis Endothelium, Vascular/cytology,metabolism Humans Neovascularization, Pathologic/etiology,metabolism Phenotype Platelet-Derived Growth Factor/metabolism Proto-Oncogene Proteins c-sis Receptors, Platelet-Derived Growth Factor/metabolism Recombinant Proteins
Chemicals
Culture Media Culture Media, Serum-Free Platelet-Derived Growth Factor Proto-Oncogene Proteins c-sis Recombinant Proteins Becaplermin DNA Receptors, Platelet-Derived Growth Factor
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Battegay E J
Department of Research and Internal Medicine, University Hospital Basel, Switzerland.
Rupp J
Iruela-Arispe L
Sage E H
Pech M
References (44)
44 references, click to expand
  1. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis.
    Microvasc Res. 1977 Jul;14(1):53-65 PMID: 895546
  2. Platelet-derived growth factor AA and AB dimers are present in normal human epithelial lining fluid.
    Eur Respir J. 1993 Sep;6(8):1162-8 PMID: 8224131
  3. Immunofluorescence and immunocytochemical procedures with affinity purified antibodies: tubulin-containing structures.
    Methods Cell Biol. 1982;24:97-132 PMID: 7048022
  4. Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle.
    Biochemistry. 1983 Mar 29;22(7):1605-13 PMID: 6303388
  5. Modulation of the sis gene transcript during endothelial cell differentiation in vitro.
    Science. 1985 May 17;228(4701):882-5 PMID: 3890179
  6. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis.
    Nature. 1985 Aug 22-28;316(6030):748-50 PMID: 4033772
  7. Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets.
    Science. 1986 Sep 5;233(4768):1078-80 PMID: 3461562
  8. Phorbol esters induce angiogenesis in vitro from large-vessel endothelial cells.
    J Cell Physiol. 1987 Feb;130(2):284-91 PMID: 2434516
  9. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  10. Inhibitory action of transforming growth factor beta on endothelial cells.
    Proc Natl Acad Sci U S A. 1987 Aug;84(16):5600-4 PMID: 2441387
  11. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class.
    Proc Natl Acad Sci U S A. 1988 May;85(10):3435-9 PMID: 2835772
  12. Transforming growth factor-beta (TGF beta) is chemotactic for human monocytes and induces their expression of angiogenic activity.
    Biochem Biophys Res Commun. 1988 Dec 15;157(2):793-800 PMID: 2462419
  13. The effects of platelet-derived growth factor in cultured microvessel endothelial cells.
    Endocrinology. 1989 Apr;124(4):1841-8 PMID: 2924726
  14. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors.
    J Biol Chem. 1989 May 25;264(15):8771-8 PMID: 2542288
  15. Purification of PDGF-AB and PDGF-BB from human platelet extracts and identification of all three PDGF dimers in human platelets.
    Biochemistry. 1990 Jan 9;29(1):166-72 PMID: 2322537
  16. Rat brain capillary endothelial cells express functional PDGF B-type receptors.
    Growth Factors. 1989;2(1):1-8 PMID: 2561393
  17. TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop.
    Cell. 1990 Nov 2;63(3):515-24 PMID: 2171777
  18. Differential expression of extracellular proteins is correlated with angiogenesis in vitro.
    Lab Invest. 1991 Feb;64(2):174-86 PMID: 1705300
  19. Human microvascular endothelial cells express receptors for platelet-derived growth factor.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):2021-5 PMID: 1848018
  20. Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation.
    J Biol Chem. 1991 May 15;266(14):8987-92 PMID: 1709159
  21. Modulation of extracellular matrix proteins by endothelial cells undergoing angiogenesis in vitro.
    Arterioscler Thromb. 1991 Jul-Aug;11(4):805-15 PMID: 1712229
  22. Multiple testing in clinical trials.
    Stat Med. 1991 Jun;10(6):871-89; discussion 889-90 PMID: 1831562
  23. Angiogenic growth factors.
    Prog Growth Factor Res. 1990;2(1):71-9 PMID: 1716501
  24. Extracellular matrix and cell shape: potential control points for inhibition of angiogenesis.
    J Cell Biochem. 1991 Nov;47(3):236-41 PMID: 1724246
  25. Platelet-derived growth factor receptors on macrovascular endothelial cells mediate relaxation via nitric oxide in rat aorta.
    J Clin Invest. 1992 Mar;89(3):878-82 PMID: 1311719
  26. Endothelial cells exhibiting angiogenesis in vitro proliferate in response to TGF-beta 1.
    J Cell Biochem. 1993 Aug;52(4):414-30 PMID: 7693728
  27. Expression of platelet-derived growth factor-beta receptors on human fibroblasts. Regulation by recombinant platelet-derived growth factor-BB, IL-1, and tumor necrosis factor-alpha.
    J Immunol. 1992 Jan 15;148(2):546-54 PMID: 1309561
  28. Angiogenesis.
    J Biol Chem. 1992 Jun 5;267(16):10931-4 PMID: 1375931
  29. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair.
    Am J Pathol. 1992 Jun;140(6):1375-88 PMID: 1376557
  30. Structural and functional studies on platelet-derived growth factor.
    EMBO J. 1992 Dec;11(12):4251-9 PMID: 1425569
  31. 1992 Mack Forster Award Lecture. Review. Regulation of angiogenesis in vitro.
    Eur J Clin Invest. 1992 Aug;22(8):504-15 PMID: 1385149
  32. Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas.
    Lab Invest. 1992 Oct;67(4):529-34 PMID: 1434531
  33. Expression of decorin by sprouting bovine aortic endothelial cells exhibiting angiogenesis in vitro.
    Exp Cell Res. 1992 Dec;203(2):395-401 PMID: 1281110
  34. Interleukin-8 as a macrophage-derived mediator of angiogenesis.
    Science. 1992 Dec 11;258(5089):1798-801 PMID: 1281554
  35. Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB.
    Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):393-7 PMID: 8380638
  36. Platelet-derived growth factor indirectly stimulates angiogenesis in vitro.
    Am J Pathol. 1993 Apr;142(4):1119-30 PMID: 7682762
  37. Tissue localization of beta receptors for platelet-derived growth factor and platelet-derived growth factor B chain during wound repair in humans.
    J Clin Invest. 1993 May;91(5):2065-75 PMID: 8486774
  38. Conservation in sequence and affinity of human and rodent PDGF ligands and receptors.
    Biochim Biophys Acta. 1993 Jun 25;1173(3):294-302 PMID: 8318539
  39. Dual role of tumor necrosis factor-alpha in angiogenesis.
    Am J Pathol. 1992 Mar;140(3):539-44 PMID: 1372154
  40. Reorganization of basement membrane matrices by cellular traction promotes the formation of cellular networks in vitro.
    Lab Invest. 1992 May;66(5):536-47 PMID: 1374138
  41. Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops.
    Cancer Res. 1992 Jun 1;52(11):3213-9 PMID: 1317261
  42. Dimerization of extracellular domains of platelet-derived growth factor receptors. A revised model of receptor-ligand interaction.
    J Biol Chem. 1993 Jul 15;268(20):15088-95 PMID: 8325884
  43. Platelet-derived growth factor is angiogenic in vivo.
    Growth Factors. 1992;7(4):261-6 PMID: 1284870
  44. Studies of morphologically atypical ("sprouting") cultures of bovine aortic endothelial cells. Growth characteristics and connective tissue protein synthesis.
    J Cell Physiol. 1980 Feb;102(2):183-91 PMID: 7189521
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.125.4.917
Published
1994-05-00
Pages
917-28
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120083
Subset
IM
Grants
NIGMS NIH HHS · GM-40711 · United States
NHLBI NIH HHS · HL-18645 · United States
External Links
PubMed source DOI: 10.1083/jcb.125.4.917 PMC Full Text View journal details
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