Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2

Barbara Margosio, Daniela Marchetti, Veronica Vergani, Raffaella Giavazzi, Marco Rusnati, Marco Presta, Giulia Taraboletti

Research output: Contribution to journalArticle

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Abstract

The antiangiogenic factor thrombospondin 1 (TSP-1) binds with high affinity to several heparin-binding angiogenic factors, including fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), and hepatocyte growth factor/scatter factor (HGF/SF). The aim of this study was to investigate whether TSP-1 affects FGF-2 association with the extracellular matrix (ECM) and its bioavailability. TSP-1 prevented the binding of free FGF-2 to endothelial cell ECM. It also promoted the mobilization of matrix-bound FGF-2, generating a TSP-1/FGF-2 complex. The region of TSP-1 responsible for these activities was located within the 140-kDa antiangiogenic and FGF-2 binding fragment, whereas the 25-kDa heparin-binding fragment was inactive. Matrix-released FGF-2/TSP-1 complex had a reduced ability to bind to and induce proliferation of endothelial cells. TSP-1 depleted the ECM laid by FGF-2-overproducing tumor cells of its FGF-2-dependent mitogenic activity for endothelial cells. Besides FGF-2, TSP-1 also inhibited VEGF and HGF/SF binding to the ECM and mobilized them from the ECM. Our study shows that TSP-1 acts as a scavenger for matrix-associated angiogenic factors, affecting their location, bioavailability, and function.

Original languageEnglish
Pages (from-to)4399-4406
Number of pages8
JournalBlood
Volume102
Issue number13
DOIs
Publication statusPublished - Dec 15 2003

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Thrombospondin 1
Fibroblast Growth Factor 2
Hepatocyte Growth Factor
Extracellular Matrix
Endothelial cells
Endothelial Cells
Angiogenesis Inducing Agents
Vascular Endothelial Growth Factor A
Biological Availability
Heparin
Tumors
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2. / Margosio, Barbara; Marchetti, Daniela; Vergani, Veronica; Giavazzi, Raffaella; Rusnati, Marco; Presta, Marco; Taraboletti, Giulia.

In: Blood, Vol. 102, No. 13, 15.12.2003, p. 4399-4406.

Research output: Contribution to journalArticle

Margosio, B, Marchetti, D, Vergani, V, Giavazzi, R, Rusnati, M, Presta, M & Taraboletti, G 2003, 'Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2', Blood, vol. 102, no. 13, pp. 4399-4406. https://doi.org/10.1182/blood-2003-03-0893
Margosio B, Marchetti D, Vergani V, Giavazzi R, Rusnati M, Presta M et al. Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2. Blood. 2003 Dec 15;102(13):4399-4406. https://doi.org/10.1182/blood-2003-03-0893
Margosio, Barbara ; Marchetti, Daniela ; Vergani, Veronica ; Giavazzi, Raffaella ; Rusnati, Marco ; Presta, Marco ; Taraboletti, Giulia. / Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2. In: Blood. 2003 ; Vol. 102, No. 13. pp. 4399-4406.
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