Constitutive NF-kappaB activity regulates the expression of VEGF and IL-8 and tumor angiogenesis of human glioblastoma.
Angiogenesis is a key pathologic feature of glioblastoma, which is the most common and most lethal primary brain tumor in adults. The degree of angiogenesis has been shown to be inversely related to patient survival. However, the molecular changes leading to angiogenesis in glioblastoma remain poorly understood. In the present study, we found a direct correlation between nuclear factor (NF)-kappaB activation and angiogenesis in glioblastomas. Blockade of NF-kappaB signaling significantly inhibited glioblastoma growth and angiogenesis in nude mice. These effects were consistent with significant inhibition of the expression of multiple angiogenic molecules, including vascular endothelial growth factor, and interleukin-8, in vitro and in vivo. Furthermore, blockade of NF-kappaB signaling also significantly inhibited the angiogenic potential of glioblastoma cells in vitro and angiogenesis of brain tumors in mouse xenograft models. Collectively, these results suggest that NF-kappaB activation plays a critical role in the growth and progression of glioblastoma and is a potential target for therapy for human glioblastoma.
Xie
Tong-Xin
TX
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Xia
Zhibo
Z
Zhang
Nu
N
Gong
Weida
W
Huang
Suyun
S
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000098:blood supply*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics*
D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A