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 language | English |
|---|---|
| Pages (from-to) | 4399-4406 |
| Number of pages | 8 |
| Journal | Blood |
| Volume | 102 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - Dec 15 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2
AU - Margosio, Barbara
AU - Marchetti, Daniela
AU - Vergani, Veronica
AU - Giavazzi, Raffaella
AU - Rusnati, Marco
AU - Presta, Marco
AU - Taraboletti, Giulia
PY - 2003/12/15
Y1 - 2003/12/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0345167898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0345167898&partnerID=8YFLogxK
U2 - 10.1182/blood-2003-03-0893
DO - 10.1182/blood-2003-03-0893
M3 - Article
C2 - 12947001
AN - SCOPUS:0345167898
VL - 102
SP - 4399
EP - 4406
JO - Blood
JF - Blood
SN - 0006-4971
IS - 13
ER -