单位：[1]Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg Surg Oncol, Los Angeles, CA 90095 USA[2]Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA[3]Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA[4]Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Hematol Oncol, Los Angeles, CA 90095 USA[5]Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA[6]Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA[7]Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA[8]Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA[9]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Neurosurg,Wuhan 430074,Hubei,Peoples R China外科学系神经内科神经外科华中科技大学同济医学院附属同济医院[10]Zhejiang Univ, Inst Canc, Hangzhou 310003, Zhejiang, Peoples R China
Glioblastoma stem cells (GSC) express both radial glial cell and neural crest cell (NCC)-associated genes. We report that endothelin 3 (EDN3), an essential mitogen for NCC development and migration, is highly produced by GSCs. Serum-induced proliferative differentiation rapidly decreased EDN3 production and downregulated the expression of stemness-associated genes, and reciprocally, two glioblastoma markers, EDN1 and YKL-40 transcripts, were induced. Correspondingly, patient glioblastoma tissues express low levels of EDN3 mRNA and high levels of EDN1 and YKL-40 mRNA. Blocking EDN3/EDN receptor B (EDNRB) signaling by an EDNRB antagonist (BQ788), or EDN3 RNA interference (siRNA), leads to cell apoptosis and functional impairment of tumor sphere formation and cell spreading/migration in culture and loss of tumorigenic capacity in animals. Using exogenous EDN3 as the sole mitogen in culture does not support GSC propagation, but it can rescue GSCs from undergoing cell apoptosis. Molecular analysis by gene expression profiling revealed that most genes downregulated byEDN3/EDNRB blockade were those involved in cytoskeleton organization, pause of growth and differentiation, and DNA damage response, implicating the involvement of EDN3/EDNRB signaling in maintaining GSC migration, undifferentiation, and survival. These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence. Mol Cancer Res; 9(12); 1668-85. (C) 2011 AACR.
基金：
American Cancer Society [RSG-07-109-01-CCE]; National Cancer Institute [1 R21 CA140912-01]; NIH [1DP2OD006444-01]; Bradley Zankel Foundation
第一作者单位：[1]Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg Surg Oncol, Los Angeles, CA 90095 USA
通讯作者：
通讯机构：[1]Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg Surg Oncol, Los Angeles, CA 90095 USA[8]Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA[*1]Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg Surg Oncol, Factor Bldg,Rm 13-260,10833 Le Conte Ave, Los Angeles, CA 90095 USA
推荐引用方式(GB/T 7714)：
Liu Yue,Ye Fei,Yamada Kazunari,et al.Autocrine Endothelin-3/Endothelin Receptor B Signaling Maintains Cellular and Molecular Properties of Glioblastoma Stem Cells[J].MOLECULAR CANCER RESEARCH.2011,9(12):1668-1685.doi:10.1158/1541-7786.MCR-10-0563.
APA：
Liu, Yue,Ye, Fei,Yamada, Kazunari,Tso, Jonathan L.,Zhang, Yibei...&Tso, Cho-Lea.(2011).Autocrine Endothelin-3/Endothelin Receptor B Signaling Maintains Cellular and Molecular Properties of Glioblastoma Stem Cells.MOLECULAR CANCER RESEARCH,9,(12)
MLA：
Liu, Yue,et al."Autocrine Endothelin-3/Endothelin Receptor B Signaling Maintains Cellular and Molecular Properties of Glioblastoma Stem Cells".MOLECULAR CANCER RESEARCH 9..12(2011):1668-1685
