Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2

Domenico Ribatti, Anna Gualandris, Mirella Belleri, Luisa Massardi, Beatrice Nico, Marco Rusnati, Patrizia Dell'era, Angelo Vacca, Luisa Roncali, Marco Presta

Research output: Contribution to journalArticle

Abstract

A close relationship exists between angiogenesis and the formation of vascular lesions. The development of the vascular system in the chick embryo chorioallantoic membrane (CAM) may thus represent a model to study the effects of the deregulation of endothelial cell behaviour. Alterations of the developing vascular tree of the CAM were observed after exposure to murine aortic endothelial (MAE) cells overexpressing human fibroblast growth factor- 2 (FGF2) cDNA (pZipFGF2 MAE cells), or to their conditioned medium (CM). pZipFGF2 MAE cells injected into the allantoic sac or applied on to the CAM of day 8-9 chick embryos induce neovascularization and the appearance of haemangioma-like lesions. This activity was not prevented by anti-FGF2 antibodies. The CM from pZipFGF2 MAE cells was also active when adsorbed into a gelatin sponge and applied on to the CAM, both in the absence and in the presence of anti-FGF2 antibodies. No effects on vessel development were exerted by parental MAE cells, FGF2-transfected NIH 3T3 fibroblasts, or their conditioned media. In vitro, pZipFGF2 MAE cell CM caused parental MAE cells to invade fibrin gels and to undergo morphogenesis on Matrigel. This activity was not mimicked by recombinant FGF2 nor affected by anti-FGF2 antibodies, and depended on a M(r)~45 000 heat-labile heparin-binding factor. Size exclusion chromatography of pZipFGF2 MAE cell CM demonstrated that the in vitro activity co-purified with an in vivo angiogenic capacity. Thus, FGF2 overexpression in mouse endothelial cells induces the production of an angiogenic activity distinct from FGF2, which may contribute to the genesis of angioproliferative lesions.

Original languageEnglish
Pages (from-to)590-599
Number of pages10
JournalJournal of Pathology
Volume189
Issue number4
DOIs
Publication statusPublished - 1999

Fingerprint

Fibroblast Growth Factor 2
Blood Vessels
Endothelial Cells
Chorioallantoic Membrane
Conditioned Culture Medium
Chick Embryo
Antibodies
Porifera
Gelatin
Hemangioma
Fibrin
Morphogenesis
Gel Chromatography
Heparin
Complementary DNA
Fibroblasts
Hot Temperature
Gels

Keywords

  • Angiogenesis
  • Chick embryo
  • Chorioallantoic membrane
  • Development
  • Fibroblast growth factor
  • Haemangioma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2. / Ribatti, Domenico; Gualandris, Anna; Belleri, Mirella; Massardi, Luisa; Nico, Beatrice; Rusnati, Marco; Dell'era, Patrizia; Vacca, Angelo; Roncali, Luisa; Presta, Marco.

In: Journal of Pathology, Vol. 189, No. 4, 1999, p. 590-599.

Research output: Contribution to journalArticle

Ribatti, D, Gualandris, A, Belleri, M, Massardi, L, Nico, B, Rusnati, M, Dell'era, P, Vacca, A, Roncali, L & Presta, M 1999, 'Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2', Journal of Pathology, vol. 189, no. 4, pp. 590-599. https://doi.org/10.1002/(SICI)1096-9896(199912)189:4<590::AID-PATH461>3.0.CO;2-W
Ribatti, Domenico ; Gualandris, Anna ; Belleri, Mirella ; Massardi, Luisa ; Nico, Beatrice ; Rusnati, Marco ; Dell'era, Patrizia ; Vacca, Angelo ; Roncali, Luisa ; Presta, Marco. / Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2. In: Journal of Pathology. 1999 ; Vol. 189, No. 4. pp. 590-599.
@article{38e83cba5e4b415e90487e715a53da77,
title = "Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2",
abstract = "A close relationship exists between angiogenesis and the formation of vascular lesions. The development of the vascular system in the chick embryo chorioallantoic membrane (CAM) may thus represent a model to study the effects of the deregulation of endothelial cell behaviour. Alterations of the developing vascular tree of the CAM were observed after exposure to murine aortic endothelial (MAE) cells overexpressing human fibroblast growth factor- 2 (FGF2) cDNA (pZipFGF2 MAE cells), or to their conditioned medium (CM). pZipFGF2 MAE cells injected into the allantoic sac or applied on to the CAM of day 8-9 chick embryos induce neovascularization and the appearance of haemangioma-like lesions. This activity was not prevented by anti-FGF2 antibodies. The CM from pZipFGF2 MAE cells was also active when adsorbed into a gelatin sponge and applied on to the CAM, both in the absence and in the presence of anti-FGF2 antibodies. No effects on vessel development were exerted by parental MAE cells, FGF2-transfected NIH 3T3 fibroblasts, or their conditioned media. In vitro, pZipFGF2 MAE cell CM caused parental MAE cells to invade fibrin gels and to undergo morphogenesis on Matrigel. This activity was not mimicked by recombinant FGF2 nor affected by anti-FGF2 antibodies, and depended on a M(r)~45 000 heat-labile heparin-binding factor. Size exclusion chromatography of pZipFGF2 MAE cell CM demonstrated that the in vitro activity co-purified with an in vivo angiogenic capacity. Thus, FGF2 overexpression in mouse endothelial cells induces the production of an angiogenic activity distinct from FGF2, which may contribute to the genesis of angioproliferative lesions.",
keywords = "Angiogenesis, Chick embryo, Chorioallantoic membrane, Development, Fibroblast growth factor, Haemangioma",
author = "Domenico Ribatti and Anna Gualandris and Mirella Belleri and Luisa Massardi and Beatrice Nico and Marco Rusnati and Patrizia Dell'era and Angelo Vacca and Luisa Roncali and Marco Presta",
year = "1999",
doi = "10.1002/(SICI)1096-9896(199912)189:4<590::AID-PATH461>3.0.CO;2-W",
language = "English",
volume = "189",
pages = "590--599",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Alterations of blood vessel development by endothelial cells overexpressing fibroblast growth factor-2

AU - Ribatti, Domenico

AU - Gualandris, Anna

AU - Belleri, Mirella

AU - Massardi, Luisa

AU - Nico, Beatrice

AU - Rusnati, Marco

AU - Dell'era, Patrizia

AU - Vacca, Angelo

AU - Roncali, Luisa

AU - Presta, Marco

PY - 1999

Y1 - 1999

N2 - A close relationship exists between angiogenesis and the formation of vascular lesions. The development of the vascular system in the chick embryo chorioallantoic membrane (CAM) may thus represent a model to study the effects of the deregulation of endothelial cell behaviour. Alterations of the developing vascular tree of the CAM were observed after exposure to murine aortic endothelial (MAE) cells overexpressing human fibroblast growth factor- 2 (FGF2) cDNA (pZipFGF2 MAE cells), or to their conditioned medium (CM). pZipFGF2 MAE cells injected into the allantoic sac or applied on to the CAM of day 8-9 chick embryos induce neovascularization and the appearance of haemangioma-like lesions. This activity was not prevented by anti-FGF2 antibodies. The CM from pZipFGF2 MAE cells was also active when adsorbed into a gelatin sponge and applied on to the CAM, both in the absence and in the presence of anti-FGF2 antibodies. No effects on vessel development were exerted by parental MAE cells, FGF2-transfected NIH 3T3 fibroblasts, or their conditioned media. In vitro, pZipFGF2 MAE cell CM caused parental MAE cells to invade fibrin gels and to undergo morphogenesis on Matrigel. This activity was not mimicked by recombinant FGF2 nor affected by anti-FGF2 antibodies, and depended on a M(r)~45 000 heat-labile heparin-binding factor. Size exclusion chromatography of pZipFGF2 MAE cell CM demonstrated that the in vitro activity co-purified with an in vivo angiogenic capacity. Thus, FGF2 overexpression in mouse endothelial cells induces the production of an angiogenic activity distinct from FGF2, which may contribute to the genesis of angioproliferative lesions.

AB - A close relationship exists between angiogenesis and the formation of vascular lesions. The development of the vascular system in the chick embryo chorioallantoic membrane (CAM) may thus represent a model to study the effects of the deregulation of endothelial cell behaviour. Alterations of the developing vascular tree of the CAM were observed after exposure to murine aortic endothelial (MAE) cells overexpressing human fibroblast growth factor- 2 (FGF2) cDNA (pZipFGF2 MAE cells), or to their conditioned medium (CM). pZipFGF2 MAE cells injected into the allantoic sac or applied on to the CAM of day 8-9 chick embryos induce neovascularization and the appearance of haemangioma-like lesions. This activity was not prevented by anti-FGF2 antibodies. The CM from pZipFGF2 MAE cells was also active when adsorbed into a gelatin sponge and applied on to the CAM, both in the absence and in the presence of anti-FGF2 antibodies. No effects on vessel development were exerted by parental MAE cells, FGF2-transfected NIH 3T3 fibroblasts, or their conditioned media. In vitro, pZipFGF2 MAE cell CM caused parental MAE cells to invade fibrin gels and to undergo morphogenesis on Matrigel. This activity was not mimicked by recombinant FGF2 nor affected by anti-FGF2 antibodies, and depended on a M(r)~45 000 heat-labile heparin-binding factor. Size exclusion chromatography of pZipFGF2 MAE cell CM demonstrated that the in vitro activity co-purified with an in vivo angiogenic capacity. Thus, FGF2 overexpression in mouse endothelial cells induces the production of an angiogenic activity distinct from FGF2, which may contribute to the genesis of angioproliferative lesions.

KW - Angiogenesis

KW - Chick embryo

KW - Chorioallantoic membrane

KW - Development

KW - Fibroblast growth factor

KW - Haemangioma

UR - http://www.scopus.com/inward/record.url?scp=0032721632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032721632&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-9896(199912)189:4<590::AID-PATH461>3.0.CO;2-W

DO - 10.1002/(SICI)1096-9896(199912)189:4<590::AID-PATH461>3.0.CO;2-W

M3 - Article

C2 - 10629563

AN - SCOPUS:0032721632

VL - 189

SP - 590

EP - 599

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 4

ER -