PMID- 12947001
OWN - NLM
STAT- MEDLINE
DCOM- 20040121
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 13
DP  - 2003 Dec 15
TI  - Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2.
PG  - 4399-406
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.
FAU - Margosio, Barbara
AU  - Margosio B
AD  - Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, 24125 
      Bergamo, Italy. taraboletti@marionegri.it
FAU - Marchetti, Daniela
AU  - Marchetti D
FAU - Vergani, Veronica
AU  - Vergani V
FAU - Giavazzi, Raffaella
AU  - Giavazzi R
FAU - Rusnati, Marco
AU  - Rusnati M
FAU - Presta, Marco
AU  - Presta M
FAU - Taraboletti, Giulia
AU  - Taraboletti G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030828
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Macromolecular Substances)
RN  - 0 (Peptide Fragments)
RN  - 0 (Thrombospondin 1)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Endothelial Cells/metabolism
MH  - Endothelium, Vascular/cytology
MH  - Extracellular Matrix/drug effects/*metabolism
MH  - Fibroblast Growth Factor 2/*metabolism
MH  - Hepatocyte Growth Factor/metabolism
MH  - Humans
MH  - Macromolecular Substances
MH  - Peptide Fragments/metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Thrombospondin 1/chemistry/*metabolism/pharmacology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2003/08/30 05:00
MHDA- 2004/01/22 05:00
CRDT- 2003/08/30 05:00
PHST- 2003/08/30 05:00 [pubmed]
PHST- 2004/01/22 05:00 [medline]
PHST- 2003/08/30 05:00 [entrez]
AID - S0006-4971(20)43943-6 [pii]
AID - 10.1182/blood-2003-03-0893 [doi]
PST - ppublish
SO  - Blood. 2003 Dec 15;102(13):4399-406. doi: 10.1182/blood-2003-03-0893. Epub 2003 
      Aug 28.