Histidine-rich glycoprotein can prevent development of mouse experimental glioblastoma.
Extensive angiogenesis, formation of new capillaries from pre-existing blood vessels, is an important feature of malignant glioma. Several antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors are currently in clinical trials as therapy for high-grade glioma and bevacizumab was recently approved by the FDA for treatment of recurrent glioblastoma. However, the modest efficacy of these drugs and emerging problems with anti-VEGF treatment resistance welcome the development of alternative antiangiogenic therapies. One potential candidate is histidine-rich glycoprotein (HRG), a plasma protein with antiangiogenic properties that can inhibit endothelial cell adhesion and migration. We have used the RCAS/TV-A mouse model for gliomas to investigate the effect of HRG on brain tumor development. Tumors were induced with platelet-derived growth factor-B (PDGF-B), in the presence or absence of HRG. We found that HRG had little effect on tumor incidence but could significantly inhibit the development of malignant glioma and completely prevent the occurrence of grade IV tumors (glioblastoma).
Kärrlander
Maria
M
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Lindberg
Nanna
N
Olofsson
Tommie
T
Kastemar
Marianne
M
Olsson
Anna-Karin
AK
Uhrbom
Lene
L
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D005822:Genetic Vectors / Q000235:genetics; D005909:Glioblastoma / Q000098:blood supply / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D006801:Humans; D007267:Injections; D051379:Mice; D009389:Neovascularization, Pathologic / Q000473:pathology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D014161:Transduction, Genetic; D000099053:Histidine-Rich Glycoprotein
D011506:Proteins; D020574:Proto-Oncogene Proteins c-sis; D000099053:Histidine-Rich Glycoprotein