CXCR4 mediates the proliferation of glioblastoma progenitor cells

被引:128
作者
Ehtesham, Moneeb [1 ,2 ]
Mapara, Khubaib Y. [1 ]
Stevenson, Charles B. [1 ]
Thompson, Reid C. [1 ,3 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Neurol Surg, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 USA
[3] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
关键词
Brain tumor(s); Glioma(s); Cancer stem cell(s); CXCR4; TUMOR STEM-CELLS; CHEMOKINE RECEPTOR; SELF-RENEWAL; GLIOMA-CELLS; EXPRESSION; PRECURSORS; SURVIVAL; GROWTH; MICROENVIRONMENT; MOBILIZATION;
D O I
10.1016/j.canlet.2008.09.034
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Increasing evidence points to a fundamental role for cancer stem cells (CSC) in the initiation and propagation of many tumors. As such, in the context of glioblastoma multiforme (GBM), the development of treatment strategies specifically targeted towards CSC-like populations may hold significant therapeutic promise. To this end, we now report that the cell surface chemokine receptor, CXCR4, a known mediator of cancer cell proliferation and invasion, is overexpressed in primary glioblastoma progenitor cells versus corresponding differentiated tumor cells. Furthermore, administration of CXCL1, the only known ligand for CXCR4, stimulates a specific and significant proliferative response in progenitors but not differentiated tumor cells. Taken together, these results implicate an important role for the CXCR4 signaling mechanism in glioma CSC biology and point to the therapeutic potential of targeting this pathway in patients with GBM. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:305 / 312
页数:8
相关论文
共 30 条
[1]   Tumor stromal-derived factor-1 recruits vascular progenitors to mitotic neovasculature, where microenvironment influences their differentiated phenotypes [J].
Aghi, Manish ;
Cohen, Kenneth S. ;
Klein, Rachael J. ;
Scadden, David T. ;
Chioccra, E. Antonio .
CANCER RESEARCH, 2006, 66 (18) :9054-9064
[2]   Self-renewal and solid tumor stem cells [J].
Al-Hajj, M ;
Clarke, MF .
ONCOGENE, 2004, 23 (43) :7274-7282
[3]   The significance of cancer cell expression of the chemokine receptor CXCR4 [J].
Balkwill, F .
SEMINARS IN CANCER BIOLOGY, 2004, 14 (03) :171-179
[4]   Glioma stem cells promote radioresistance by preferential activation of the DNA damage response [J].
Bao, Shideng ;
Wu, Qiulian ;
McLendon, Roger E. ;
Hao, Yueling ;
Shi, Qing ;
Hjelmeland, Anita B. ;
Dewhirst, Mark W. ;
Bigner, Darell D. ;
Rich, Jeremy N. .
NATURE, 2006, 444 (7120) :756-760
[5]   Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor [J].
Bao, Shideng ;
Wu, Qiulian ;
Sathornsumetee, Sith ;
Hao, Yueling ;
Li, Zhizhong ;
Hjelmeland, Anita B. ;
Shi, Oing ;
McLendon, Roger E. ;
Bigner, Darell D. ;
Rich, Jeremy N. .
CANCER RESEARCH, 2006, 66 (16) :7843-7848
[6]  
Barbero S, 2003, CANCER RES, V63, P1969
[7]   CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment [J].
Burger, JA ;
Kipps, TJ .
BLOOD, 2006, 107 (05) :1761-1767
[8]   Self-renewal and solid-tumor stem cells [J].
Clarke, MF .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2005, 11 (02) :14-16
[9]   A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors [J].
Dziembowska, M ;
Tham, TN ;
Lau, P ;
Vitry, S ;
Lazarini, F ;
Dubois-Dalcq, M .
GLIA, 2005, 50 (03) :258-269
[10]   Ligand-dependent activation of the hedgehog pathway in glioma progenitor cells [J].
Ehtesham, M. ;
Sarangi, A. ;
Valadez, J. G. ;
Chanthaphaychith, S. ;
Becher, M. W. ;
Abel, T. W. ;
Thompson, R. C. ;
Cooper, M. K. .
ONCOGENE, 2007, 26 (39) :5752-5761