VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells.
There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo. Although VEGF did not affect the property of CSCs in vitro, the injection of mouse brains with VEGF-expressing CSCs led to the massive expansion of vascular-rich GBM, tumor-associated hemorrhage, and high morbidity, suggesting that VEGF promoted tumorigenesis via angiogenesis. These results revealed that VEGF induced the proliferation of VEC in the vascular-rich tumor environment, the so-called stem cell niche.
Oka
Naoki
N
Department of Neurosurgery, Gifu University School of Medicine, 1-1 Yanagido, Gifu City, Gifu 501-1194, Japan.
Soeda
Akio
A
Inagaki
Akihito
A
Onodera
Masafumi
M
Maruyama
Hidekazu
H
Hara
Akira
A
Kunisada
Takahiro
T
Mori
Hideki
H
Iwama
Toru
T
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005909:Glioblastoma / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D042461:Vascular Endothelial Growth Factor A