Basic fibroblast growth factor overexpression in endothelial cells: An autocrine mechanism for angiogenesis and angioproliferative diseases

Anna Gualandris, Marco Rusnati, Mirella Belleri, Enrico Emanuele Nelli, Maria Bastaki, Maria Pia Molinari-Tosatti, Fabrizio Bonardi, Silvia Parolini, Adriana Albini, Lucia Morbidelli, Marina Ziche, Alfredo Corallini, Laura Possati, Angelo Vacca, Domenico Ribatti, Marco Presta

Research output: Contribution to journalArticle

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Abstract

Basic fibroblast growth factor (bFGF) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases. The ultimate significance of this observation is poorly understood. We have investigated the biological consequences of endothelial cell activation by endogenous bFGF in a mouse aortic endothelial cell line stably transfected with a retroviral expression vector harboring a human bFGF cDNA. Selected clones expressing M(r) 24,000, M(r) 22,000, and/or M(r) 18,000 bFGF isoforms were characterized by a transformed morphology and an increased saturation density. bFGF transfectants showed invasive behavior and sprouting activity in three- dimensional fibrin gels and formed a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on laminin-rich basement membrane matrix (Matrigel). The invasive and morphogenetic behavior was prevented by anti-bFGF antibody, revealing the autocrine modality of the process. The biological consequences of this autocrine activation were investigated in vivo. bFGF-transfected cells gave rise to highly vascularized lesions resembling Kaposi's sarcoma when injected in nude mice and induced angiogenesis in avascular rabbit cornea. When injected into the allantoic sac of the chick embryo, they caused an increase in vascular density and formation of hemangiomas in the chorioallantoic membrane. In conclusion, bFGF-overexpressing endothelial cells acquire an angiogenic phenotype and recruit quiescent endothelium originating angioproliferative lesions in vivo. These findings demonstrate that bFGF overexpression exerts an autocrine role for endothelial cells and support the notion that tumor neovascularization and angioproliferative diseases can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).

Original languageEnglish
Pages (from-to)147-160
Number of pages14
JournalCell Growth and Differentiation
Volume7
Issue number2
Publication statusPublished - Feb 1996

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Fibroblast Growth Factor 2
Endothelial Cells
Vascular Endothelium
Chorioallantoic Membrane
Kaposi's Sarcoma
Laminin
Chick Embryo
Hemangioma
Fibrin
Basement Membrane
Nude Mice
Cornea
Endothelium
Blood Vessels
Neoplasms
Protein Isoforms
Complementary DNA
Clone Cells
Gels
Rabbits

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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Basic fibroblast growth factor overexpression in endothelial cells : An autocrine mechanism for angiogenesis and angioproliferative diseases. / Gualandris, Anna; Rusnati, Marco; Belleri, Mirella; Nelli, Enrico Emanuele; Bastaki, Maria; Molinari-Tosatti, Maria Pia; Bonardi, Fabrizio; Parolini, Silvia; Albini, Adriana; Morbidelli, Lucia; Ziche, Marina; Corallini, Alfredo; Possati, Laura; Vacca, Angelo; Ribatti, Domenico; Presta, Marco.

In: Cell Growth and Differentiation, Vol. 7, No. 2, 02.1996, p. 147-160.

Research output: Contribution to journalArticle

Gualandris, A, Rusnati, M, Belleri, M, Nelli, EE, Bastaki, M, Molinari-Tosatti, MP, Bonardi, F, Parolini, S, Albini, A, Morbidelli, L, Ziche, M, Corallini, A, Possati, L, Vacca, A, Ribatti, D & Presta, M 1996, 'Basic fibroblast growth factor overexpression in endothelial cells: An autocrine mechanism for angiogenesis and angioproliferative diseases', Cell Growth and Differentiation, vol. 7, no. 2, pp. 147-160.
Gualandris, Anna ; Rusnati, Marco ; Belleri, Mirella ; Nelli, Enrico Emanuele ; Bastaki, Maria ; Molinari-Tosatti, Maria Pia ; Bonardi, Fabrizio ; Parolini, Silvia ; Albini, Adriana ; Morbidelli, Lucia ; Ziche, Marina ; Corallini, Alfredo ; Possati, Laura ; Vacca, Angelo ; Ribatti, Domenico ; Presta, Marco. / Basic fibroblast growth factor overexpression in endothelial cells : An autocrine mechanism for angiogenesis and angioproliferative diseases. In: Cell Growth and Differentiation. 1996 ; Vol. 7, No. 2. pp. 147-160.
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T2 - An autocrine mechanism for angiogenesis and angioproliferative diseases

AU - Gualandris, Anna

AU - Rusnati, Marco

AU - Belleri, Mirella

AU - Nelli, Enrico Emanuele

AU - Bastaki, Maria

AU - Molinari-Tosatti, Maria Pia

AU - Bonardi, Fabrizio

AU - Parolini, Silvia

AU - Albini, Adriana

AU - Morbidelli, Lucia

AU - Ziche, Marina

AU - Corallini, Alfredo

AU - Possati, Laura

AU - Vacca, Angelo

AU - Ribatti, Domenico

AU - Presta, Marco

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N2 - Basic fibroblast growth factor (bFGF) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases. The ultimate significance of this observation is poorly understood. We have investigated the biological consequences of endothelial cell activation by endogenous bFGF in a mouse aortic endothelial cell line stably transfected with a retroviral expression vector harboring a human bFGF cDNA. Selected clones expressing M(r) 24,000, M(r) 22,000, and/or M(r) 18,000 bFGF isoforms were characterized by a transformed morphology and an increased saturation density. bFGF transfectants showed invasive behavior and sprouting activity in three- dimensional fibrin gels and formed a complex network of branching cord-like structures connecting foci of infiltrating cells when seeded on laminin-rich basement membrane matrix (Matrigel). The invasive and morphogenetic behavior was prevented by anti-bFGF antibody, revealing the autocrine modality of the process. The biological consequences of this autocrine activation were investigated in vivo. bFGF-transfected cells gave rise to highly vascularized lesions resembling Kaposi's sarcoma when injected in nude mice and induced angiogenesis in avascular rabbit cornea. When injected into the allantoic sac of the chick embryo, they caused an increase in vascular density and formation of hemangiomas in the chorioallantoic membrane. In conclusion, bFGF-overexpressing endothelial cells acquire an angiogenic phenotype and recruit quiescent endothelium originating angioproliferative lesions in vivo. These findings demonstrate that bFGF overexpression exerts an autocrine role for endothelial cells and support the notion that tumor neovascularization and angioproliferative diseases can be triggered by stimuli that induce vascular endothelium to produce its own autocrine factor(s).

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