Angiogenesis in malignant gliomas.
One event that accompanies glioma progression is the upregulation of angiogenesis. Low-grade gliomas are moderately vascularized tumors whereas high-grade gliomas show prominent microvascular proliferations and areas of high vascular density. To analyze the molecular mechanisms underlying glioma angiogenesis, we studied the expression of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors VEGFR-1 and VEGFR-2 during normal brain development and glioma-induced angiogenesis. Our results suggest a paracrine control of angiogenesis and endothelial cell proliferation that is tightly regulated and transient in the embryonic brain, switched off in the normal adult brain, and turned on in tumor cells (VEGF) and the host vasculature (VEGFR-1 and -2) during tumor progression. It is unknown how VEGF and VEGF receptors are upregulated during glioma angiogenesis, but there is recent evidence that VEGF as well as endogenous inhibitors of angiogenesis could be under control of the tumor suppressor genes p53 and VHL.
Plate
K H
KH
Neurozentrum, Albert-Ludwigs Universität, Freiburg, Germany.
Risau
W
W
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D005910:Glioma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D012039:Regional Blood Flow / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A
D016228:Endothelial Growth Factors; D006023:Glycoproteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor