PMID- 9988225
OWN - NLM
STAT- MEDLINE
DCOM- 19990223
LR  - 20230124
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 84
IP  - 1
DP  - 1999 Feb 19
TI  - Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter 
      factor and basic fibroblast growth factor in human gliomas and their relation to 
      angiogenesis.
PG  - 10-8
AB  - Angiogenesis is a possible target in the treatment of human gliomas. To evaluate 
      the role of 3 growth factors, vascular endothelial growth factor (VEGF), 
      hepatocyte growth factor/scatter factor (HGF/SF) and basic fibroblast growth 
      factor (bFGF), in the angiogenic cascade, we determined their levels in extracts 
      of 71 gliomas by enzyme-linked immunosorbent assay (ELISA). The levels of bFGF 
      were only marginally different between gliomas of World Health Organization (WHO) 
      grade II (low grade) and grades III and IV (high grade). In contrast, the mean 
      concentrations of VEGF were 11-fold higher in high-grade tumors and those of 
      HGF/SF 7-fold, respectively. Both were highly significantly correlated with 
      microvessel density (p < 0.001) as determined by immunostaining for factor 
      VIII-related antigen. In addition, VEGF and HGF/SF appeared to be independent 
      predictive parameters for glioma microvessel density as determined by multiple 
      regression analysis. We measured the capacity of all 3 factors to induce 
      endothelial tube formation in a collagen gel. In this assay, bFGF was found to be 
      an essential cofactor with which VEGF as well as HGF/SF were able to synergize 
      independently. According to the concentrations of angiogenic factors, extracts 
      from high-grade tumors were significantly more potent in the tube formation assay 
      than the low-grade extracts (p = 0.02). Adding neutralizing antibodies to bFGF, 
      VEGF and HGF/SF together with the extracts, tube formation was inhibited by up to 
      98%, 62% and 54%, respectively. Our findings suggest that bFGF is an essential 
      cofactor for angiogenesis in gliomas, but in itself is insufficient as it is 
      present already in the sparsely vascularized low-grade tumors. Upon induction of 
      angiogenesis in high-grade tumors, bFGF may synergize with rising levels of not 
      only VEGF but possibly also with HGF/SF, which appears here to be an independent 
      angiogenic factor.
FAU - Schmidt, N O
AU  - Schmidt NO
AD  - Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany.
FAU - Westphal, M
AU  - Westphal M
FAU - Hagel, C
AU  - Hagel C
FAU - Ergun, S
AU  - Ergun S
FAU - Stavrou, D
AU  - Stavrou D
FAU - Rosen, E M
AU  - Rosen EM
FAU - Lamszus, K
AU  - Lamszus K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Cells, Cultured
MH  - Chemotaxis/drug effects
MH  - Endothelial Growth Factors/*metabolism
MH  - Endothelium, Vascular/metabolism/physiology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblast Growth Factor 2/*metabolism
MH  - Glioma/blood supply/*metabolism
MH  - Hepatocyte Growth Factor/*metabolism
MH  - Humans
MH  - Lymphokines/*metabolism
MH  - Microcirculation/drug effects
MH  - *Neovascularization, Pathologic
MH  - Recombinant Proteins/metabolism/pharmacology
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1999/02/13 03:14
MHDA- 2000/06/20 09:00
CRDT- 1999/02/13 03:14
PHST- 1999/02/13 03:14 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/02/13 03:14 [entrez]
AID - 10.1002/(SICI)1097-0215(19990219)84:1<10::AID-IJC3>3.0.CO;2-L [pii]
AID - 10.1002/(sici)1097-0215(19990219)84:1<10::aid-ijc3>3.0.co;2-l [doi]
PST - ppublish
SO  - Int J Cancer. 1999 Feb 19;84(1):10-8. doi: 
      10.1002/(sici)1097-0215(19990219)84:1<10::aid-ijc3>3.0.co;2-l.