title: Survivin promotes glioma angiogenesis through vascular endothelial growth factor and basic fibroblast growth factor in vitro and in vivo.
abstract: Survivin is involved in multiple signaling mechanisms in tumor maintenance, and accumulated studies elucidate that knockdown of survivin in endothelial cells could inhibit angiogenesis; however, the role of survivin in tumor cells to regulate tumor-derived angiogenesis remains largely unclear. In the present study 80 cases of brain glioma were chosen and protein expressions of survivin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) in glioma cells were investigated by immunohistochemistry (IHC). Human umbilical vein endothelial cells (HUVEC) were cocultured with human glioma U251 wild-type cells, U251 cells survivin silenced, SHG44 wild-type cells, and SHG44 survivin-overexpressing cells, respectively. The proliferation and migration of HUVEC were evaluated by MTT assay and transwell chamber assay. The microvessels density (MVD) marked by CD31 expression in vascular endothelial cells in glioma xenografts in nude mice was detected by IHC. VEGF, bFGF, and PDGF in the aforementioned cells were detected by quantitive PCR (qPCR), Western blot, ELISA, and IHC in vitro and in vivo. The results showed that VEGF immunoreactivity score (IRS), bFGF IRS, and PDGF IRS were all positively correlated with survivin IRS in gliomas, respectively (P < 0.01). Survivin in human glioma cells could significantly promote the proliferation and migration of HUVEC and increase MVD, which could be contributed to survivin-dependent burst of VEGF and bFGF expression, followed by increase of tumor growth and proliferation. In summary, survivin, through upregulation of VEGF and bFGF, plays an essential role during glioma angiogenesis.
authors.affiliation: Department of Neurosurgery of Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Haining
authors.initials: H
authors.lastname: Zhen
authors.forename: Jiashu
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.forename: Geng
authors.initials: G
authors.lastname: Guo
authors.forename: Xinggang
authors.initials: X
authors.lastname: Mao
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000098:blood supply*; D045744:Cell Line, Tumor; D017931:DNA Primers; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005910:Glioma / Q000098:blood supply*; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2