IGFBP2 promotes glioma tumor stem cell expansion and survival

被引：61
作者：
Hsieh, David [1 ]
Hsieh, Antony [2 ]
Stea, Baldassarre [3 ]
Ellsworth, Ron [1 ]
机构：
[1] Univ Arizona, Coll Med, Tucson, AZ 85721 USA
[2] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA
[3] Univ Arizona, Dept Radiat Oncol, Tucson, AZ 85721 USA
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 397卷 / 02期
关键词：
Glioblastoma; IGF; Tumor stem cell; IGFBP2; FACTOR-BINDING PROTEIN-2; HIGH-GRADE GLIOMAS; HUMAN GLIOBLASTOMA; CANCER CELLS; GROWTH; EXPRESSION; PROLIFERATION; PROGRESSION; MECHANISMS; SYSTEM;
D O I：
10.1016/j.bbrc.2010.05.145
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
IGFBP2 is overexpressed in the most common brain tumor, glioblastoma (GBM), and its expression is inversely correlated to GBM patient survival. Previous reports have demonstrated a role for IGFBP2 in glioma cell invasion and astrocytoma development. However, the function of IGFBP2 in the restricted, self-renewing, and tumorigenic GBM cell population comprised of tumor-initiating stem cells has yet to be determined. Herein we demonstrate that IGFBP2 is overexpressed within the stem cell compartment of GBMs and is integral for the clonal expansion and proliferative properties of glioma stem cells (GSCs). In addition, IGFBP2 inhibition reduced Akt-dependent GSC genotoxic and drug resistance. These results suggest that IGFBP2 is a selective malignant factor that may contribute significantly to GBM pathogenesis by enriching for GSCs and mediating their survival. Given the current dearth of selective molecular targets against GSCs, we anticipate our results to be of high therapeutic relevance in combating the rapid and lethal course of GBM. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码：367 / 372
页数：6
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