DETECTION AND QUANTIFICATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR IN BRAIN-TUMOR TISSUE AND CYST FLUID - THE KEY TO ANGIOGENESIS

被引:149
作者
WEINDEL, K
MORINGLANE, JR
MARME, D
WEICH, HA
机构
[1] GESELL BIOTECHNOL FORSCH MBH, DEPT GENE EXPRESS, D-38124 BRAUNSCHWEIG, GERMANY
[2] UNIV FREIBURG, CTR TUMOR BIOL, INST MOLEC MED, D-79106 FREIBURG, GERMANY
[3] UNIV SAARLAND, DEPT NEUROSURG, STEREOTAXY SECT, W-6650 HOMBURG, GERMANY
关键词
ANGIOGENESIS; CYST FLUID; GLIOBLASTOMAS; VASCULAR ENDOTHELIAL GROWTH FACTOR; VASCULAR PERMEABILITY FACTOR;
D O I
10.1227/00006123-199409000-00012
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
IN PRIMARY MALIGNANT brain tumors increased vascularity and marked edema strongly suggest a possible role of the vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). This was confirmed by earlier in situ hybridization studies, by analysis of the expression of the mitogen in different subsets of glioblastoma cells, and by the fact that the VEGF/VPF receptor flt-1 (fms-like tyrosine kinase) is up-regulated in tumor cells in vivo. To assess and quantify the expression of the VEGF/VPF gene and of the receptor gene, 26 surgical specimens of brain tumor tissue from 24 patients were analyzed. In most malignant gliomas, the expression level of the VEGF/VPF gene is elevated and can be increased up to 20- to 50-fotd in comparison with low-grade tumors. Using polymerase chain reaction-based amplification, it could be shown that the messenger RNAs of three different VEGF/VPF forms are synthesized in tumor tissue samples. Northern blot studies revealed that in some samples a significant expression of the gene coding for placenta growth factor, a growth factor closely related to VEGF/VPF, was observed. In addition, using a radioreceptor assay it was possible to detect high VEGF/VPF-like activity in the cyst fluids of brain tumors, indicating the accumulation of the mitogen and permeability factor in brain tumor cysts. Further investigations revealed that astrocytoma and glioblastoma cells in culture express the VEGF/VPF gene and secrete the VEGF/VPF protein, whereas gene expression of the two known VEGF/VPF receptors, kinase insert domain-containing receptor and flt-1, could not be detected. These data support previous reports, which stated that VEGF/VPF acts as a paracrine growth and permeability factor in brain tumors and may contribute to tumor growth by initiating tumor angiogenesis.
引用
收藏
页码:439 / 448
页数:10
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