Platelet-derived Growth Factor-BB and Basic Fibroblast Growth Factor Directly Interact in Vitro with High Affinity

Russo, Katia; Ragone, Raffaele; Facchiano, Angelo; Capogrossi, Maurizio C.; Facchiano, Antonio

doi:10.1074/jbc.m108858200

Cited by 30 publications

(32 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent evidence shows that PDGF-BB and bFGF directly interact with high affinity, 70 and this may, at least in part, explain the observed inhibitory effect.…”

Section: Discussionmentioning

confidence: 99%

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Marchis

Ribatti

Giampietri

et al. 2002

Blood

Self Cite

View full text Add to dashboard Cite

Basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) modulate vascular wall cell function in vitro and angiogenesis in vivo. The aim of the current study was to determine how bovine aorta endothelial cells (BAECs) respond to the simultaneous exposure to PDGF-BB and bFGF. It was found that bFGF-dependent BAEC migration, proliferation, and differentiation into tubelike structures on reconstituted extracellular matrix (Matrigel) were inhibited by PDGF-BB. The role played by PDGF receptor ␣ (PDGF-R␣) was investigated by selective stimulation with PDGF-AA, by blocking PDGF-BB-binding to PDGF-R␣ with neomycin, or by transfecting cells with dominant-negative forms of the receptors to selectively impair either PDGF-R␣ or PDGF-R␤ function. In all cases, PDGF-R␣ impairment abolished the inhibitory effect of PDGF-BB on bFGF-directed BAEC migration. In addition, PDGF-R␣ phosphorylation was increased in the presence of bFGF and PDGF, as compared to PDGF alone, whereas mitogen-activated protein kinase phosphorylation was decreased in the presence of PDGF-BB and bFGF compared with bFGF alone. In vivo experiments showed that PDGF-BB and PDGF-AA inhibited bFGF-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane assay and that PDGF-BB inhibited bFGF-induced angiogenesis in Matrigel plugs injected subcutaneously in CD1 mice. Taken IntroductionThe endothelial layer represents a physical and chemical barrier between the vessel lumen and the underlying tissues. Endothelial cells (ECs) exert a variety of functions and modulate underlying smooth muscle cells by releasing molecules with vasoactive and growth-regulatory properties. 1 Endothelial cells present an active replication phenotype in vitro, but in vivo they are quiescent. 2 The different expression of membrane-bound receptors 3,4 and the in vivo action of specific inhibitors 5-7 may account, at least in part, for the different replication pattern observed.Basic fibroblast growth factor (bFGF) is a potent EC growth factor; it is known to induce a proangiogenic phenotype in ECs and is released under acidosis conditions that induce EC protection from apoptosis. 8 bFGF plays a critical role in physiologic and pathologic angiogenesis, including tumor angiogenesis. 9,10 It exerts its functions by direct action, 11 by inducing vascular endothelial growth factor (VEGF) synthesis, 12 or by potentiating VEGF activity. 13,14 Platelet-derived growth factor (PDGF) is a growth factor known to be active on ECs. Three PDGF isoforms have been identified as disulfide-linked dimers, namely PDGF-AA, PDGF-BB, and PDGF-AB, expressed by ECs under various conditions. 15-19 They interact with different affinity with 2 tyrosine-kinase receptors, PDGF-R␣ and PDGF-R␤, which are expressed on ECs in normal 4,20-22 and in pathologic conditions. [23][24][25][26] Recently, PDGF-C and PDGF-D isoforms were also identified. 27,28 PDGF isoforms are reported to exert mitogenic and chemotactic action on EC, although PDGF-AA appears to be less potent or inactive...

show abstract

“…Recent evidence shows that PDGF-BB and bFGF directly interact with high affinity, 70 and this may, at least in part, explain the observed inhibitory effect.…”

Section: Discussionmentioning

confidence: 99%

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Marchis

Ribatti

Giampietri

et al. 2002

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…Platelet-derived growth factor BB (PDGF-BB) binds FGF2 in a 1:2 stoichiometry [168]. This interaction may contribute to the inhibitory effect exerted by PDGF-BB on FGF2-dependent neovascularization [169].…”

Section: Cytokinesmentioning

confidence: 99%

“…Since then, 22 structurally-related members of the FGF family have been identified [8]. FGFs are pleiotropic factors acting on different cell types, including www.elsevier.com/locate/cytogfr Cytokine & Growth Factor Reviews 16 (2005) [159][160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178] endothelial cells, following interaction with heparan-sulfate proteoglycans (HSPGs) and tyrosine kinase FGF receptors (FGFRs). To date, more than 1200 PubMed-referenced papers related to FGFs and FGFRs in endothelial cells and during neovascularization have been published.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Presta

Dell’Era

Mitola

et al. 2005

Cytokine & Growth Factor Reviews

1,129

870

View full text Add to dashboard Cite

Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer. Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization. #

show abstract

“…The role of PDGF-R␣ is somehow more complex because it triggers inducing signals and inhibitory signals. 14,16 We previously showed, both in vitro and in vivo, that FGF-2 and PDGF-BB interact with high affinity, 14 leading to reciprocal inhibitory effects mediated, at least in part, by PDFG-R␣ and FGF-R1. 13,34 These data represent the first evidence indicating that PDGF-BB may acquire in vivo antiangiogenic effects mediated by PDGF-R␣ and highlight that PDGF activity may be controlled or even counteracted by the expression levels and activation state of the corresponding ␣ and ␤ receptors.…”

Section: Fret Confocal Analysismentioning

confidence: 99%

“…8 Although the PDGF family is known to exert mitogenic and chemotactic action, PDGF-AA and PDGF-R␣ are less potent or even inhibitory molecules on endothelial and vascular cells, as we and others have shown. [9][10][11][12][13] We have previously observed a direct in vitro high-affinity FGF-2/PDGF-BB interaction 14 and strong FGF-2 inhibition both in vitro and in vivo in the presence of either PDGF-BB or PDGF-AA, through a PDGF-R␣-mediated mechanism. 13 Consistent with these data, other groups have shown that PDGF-R␣ may activate positive and negative signals 15 mediated by JNK-1 and p21WAF/CIP1 promoter induction.…”

Section: Introductionmentioning

confidence: 99%

Heterodimerization of FGF-receptor 1 and PDGF-receptor-α: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells

Faraone

Aguzzi

Ragone

et al. 2006

Blood

Self Cite

View full text Add to dashboard Cite

Previous evidence has shown that platelet-derived growth factor-BB (PDGF-BB) and fibroblast growth factor-2 (FGF-2) directly interact with high affinity, leading to potent reciprocal inhibitory effects on bovine endothelial cells and rat vascular smooth muscle cells. In this study, we report that PDGF-BB inhibits a series of FGF-2-induced events, such as proliferation of human umbilical vein endothelial cells (

show abstract

Platelet-derived Growth Factor-BB and Basic Fibroblast Growth Factor Directly Interact in Vitro with High Affinity

Cited by 30 publications

References 78 publications

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Platelet-derived growth factor inhibits basic fibroblast growth factor angiogenic properties in vitro and in vivo through its α receptor

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

Heterodimerization of FGF-receptor 1 and PDGF-receptor-α: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells

Contact Info

Product

Resources

About