title: Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a key role in vasculogenic mimicry formation, neovascularization and tumor initiation by Glioma stem-like cells.
abstract: Human glioblastomas (GBM) are thought to be initiated by glioma stem-like cells (GSLCs). GSLCs also participate in tumor neovascularization by transdifferentiating into vascular endothelial cells. Here, we report a critical role of GSLCs in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed vascular endothelial growth factor receptor-2 (VEGFR-2) that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. Knockdown of VEGFR-2 in GSLCs by shRNA markedly reduced their capacity of self-renewal, forming tubules, initiating xenograft tumors, promoting vascularization and the establishment of VM. Our study demonstrates VEGFR-2 as an essential molecule to sustain the "stemness" of GSLCs, their capacity to initiate tumor vasculature, and direct initiation of tumor.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Third Military Medical University, Chongqing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yao
authors.forename: Yifang
authors.initials: Y
authors.lastname: Ping
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Kequiang
authors.initials: K
authors.lastname: Chen
authors.forename: Teizo
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Mingyong
authors.initials: M
authors.lastname: Liu
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.forename: Qin
authors.initials: Q
authors.lastname: Niu
authors.forename: Deyu
authors.initials: D
authors.lastname: Guo
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.forename: Xiuwu
authors.initials: X
authors.lastname: Bian
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
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