Vascular endothelial growth factor, hepatocyte growth factor/scatter factor, basic fibroblast growth factor, and placenta growth factor in human meningiomas and their relation to angiogenesis and malignancy.
OBJECTIVE
Angiogenesis is mediated by a number of different growth factors and appears vital for tumor growth. The understanding of angiogenic mechanisms could offer new therapeutic perspectives; in this context, the role of four potentially angiogenic growth factors was analyzed in a large series of meningiomas of different grades.


METHODS
Vascular endothelial growth factor (VEGF), placenta growth factor, hepatocyte growth factor/scatter factor, and basic fibroblast growth factor were quantified in 69 tumors by enzyme-linked immunosorbent assay. Microvessel density and proliferative activity were determined on paraffin sections, and clinical tumor invasiveness was rated. Induction of endothelial chemotaxis and capillary-like tube formation were studied in vitro using modified Boyden chamber assays and three-dimensional collagen gel assays, respectively.


RESULTS
Tumors included 40 benign (World Health Organization [WHO] Grade I), 21 atypical (WHO Grade II), and 8 anaplastic/malignant (WHO Grade III) meningiomas. We found a correlation between meningioma grade and VEGF content (r = 0.37, P = 0.002), which was 2-fold higher in atypical than in benign meningiomas (P = 0.022) and 10-fold higher in malignant than in benign meningiomas (P = 0.025). Among different subtypes of Grade I meningiomas, VEGF levels were 10-fold higher in meningothelial than in fibrous meningiomas (P = 0.015). None of the other three factors investigated showed any association with tumor grade, microvessel density, or invasiveness, and VEGF also did not correlate with vascularity or invasiveness. Moreover, vascularity did not increase with malignancy grade. Endothelial chemotaxis and capillary-like tube formation in vitro were induced by meningioma extracts and were most effectively blocked by co-addition of antibodies against basic fibroblast growth factor, followed by anti-VEGF, whereas anti-hepatocyte growth factor/scatter factor was not effective. The chemotactic activity of meningioma extracts on endothelial cells correlated with their VEGF content (r = 0.6, P = 0.003).


CONCLUSIONS
Meningiomas do not show an angiogenic switch involving VEGF and/or hepatocyte growth factor/scatter factor, as has previously been found in gliomas. Nevertheless, the biological activity of VEGF and basic fibroblast growth factor in meningiomas suggests that both are potential targets for antiangiogenic therapy in meningiomas of all WHO grades.
Lamszus
K
K
Department of Neuropathology, University Hospital Eppendorf, Hamburg, Germany.
Lengler
U
U
Schmidt
N O
NO
Stavrou
D
D
Ergün
S
S
Westphal
M
M
D002633:Chemotaxis; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008577:Meningeal Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D014020:Tissue Extracts / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D014020:Tissue Extracts; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D000072483:Placenta Growth Factor; D017228:Hepatocyte Growth Factor