The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell‐mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling

Yi‐fang Ping; Xiao‐Hong Yao; Jian‐yong Jiang; Lin‐tao Zhao; Shi‐cang Yu; Tao Jiang; Marie CM Lin; Jian‐hong Chen; Bin Wang; Rong Zhang; You‐Hong Cui; Cheng Qian; Ji Ming Wang; Xiu‐Wu Bian

doi:10.1002/path.2908

journal article May 27, 2011

The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell‐mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling

Yi‐fang Ping Xiao‐Hong Yao Jian‐yong Jiang Lin‐tao Zhao Shi‐cang Yu Tao Jiang

Marie CM Lin Jian‐hong Chen Bin Wang

Rong Zhang

You‐Hong Cui Cheng Qian

Ji Ming Wang

Xiu‐Wu Bian

The Journal of Pathology Vol. 224 No. 3 pp. 344-354 · Wiley

View at Publisher Save 10.1002/path.2908

Abstract

AbstractChemokines and their receptors are actively involved in inflammation, immune responses, and cancer development. Here we report the detection of CD133+ glioma stem‐like cells (GSCs) co‐expressing a chemokine receptor CXCR4 in human primary glioma tissues. These GSCs were located in areas adjacent to tumour vascular capillaries, suggesting an association between GSCs and tumour angiogenesis. To test this hypothesis, we isolated CD133+ GSCs from surgical specimens of human primary gliomas and glioma cell lines. As compared to CD133− cells, CD133+ GSCs expressed significantly higher levels of CXCR4 mRNA and protein, and migrated more efficiently in response to the CXCR4 ligand CXCL12. In addition, CXCL12 induced vascular endothelial growth factor (VEGF) production by CD133+ GSCs via activation of the PI3K/AKT signalling pathway. Furthermore, knocking down of CXCR4 using RNA interference or inhibition of CXCR4 function by an antagonist AMD3100 not only reduced VEGF production by CD133+ GSCs in vitro, but also attenuated the growth and angiogenesis of tumour xenografts in vivo formed by CD133+ GSCs in SCID mice. These results indicate that CXCL12 and its receptor CXCR4 promote GSC‐initiated glioma growth and angiogenesis by stimulating VEGF production. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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References

54

[1]

10.1158/0008-5472.can-05-3153

[2]

10.1146/annurev.cellbio.22.010305.104154

[3]

10.1158/0008-5472.can-06-3126

[4]

Identification of human brain tumour initiating cells

Sheila K. Singh, Cynthia Hawkins, Ian D. Clarke et al.

Nature 10.1038/nature03128

[5]

Singh SK "Identification of a cancer stem cell in human brain tumours" Cancer Res (2003)

[6]

10.1038/modpathol.3800942

[7]

10.1073/pnas.0307618100

[8]

10.1016/j.canlet.2008.02.010

[9]

Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma

Gentao Liu, Xiangpeng Yuan, Zhaohui Zeng et al.

Molecular Cancer 10.1186/1476-4598-5-67

[10]

10.1073/pnas.0400067101

[11]

10.1038/nature05236

[12]

10.1002/path.2356

[13]

Ping YF "Activation of CXCR4 in human glioma stem cells promotes tumour angiogenesis" Zhonghua Bing Li Xue Za Zhi (2007)

[14]

10.1158/0008-5472.can-06-1010

[15]

10.2174/156652411794474383

[16]

10.1158/0008-5472.can-09-0167

[17]

10.2741/2930

[18]

10.1016/j.canlet.2008.03.014

[19]

10.1227/01.neu.0000290905.53685.a2

[20]

10.1227/01.neu.0000324896.26088.ef

[21]

10.1158/1078-0432.ccr-06-1372

[22]

Kleihues P (2007)

[23]

10.1371/journal.pone.0011316

[24]

10.1093/jnci/dji142

[25]

10.1371/journal.pone.0010786

[26]

10.1007/s11060-007-9349-8

[27]

10.1002/pmic.200700054

[28]

10.1038/nrg1323

[29]

10.1002/glia.20414

[30]

10.1158/0008-5472.can-09-0167

[31]

10.1016/j.ccr.2006.11.020

[32]

10.1007/s00432-009-0578-4

[33]

10.1016/j.mcn.2008.07.022

[34]

10.1038/31261

[35]

10.1634/stemcells.2004-0342

[36]

10.1006/dbio.1999.9405

[37]

10.1096/fj.03-0935fje

[38]

10.1227/01.neu.0000316019.28421.95

[39]

10.1158/0008-5472.can-05-0626

[40]

10.1016/j.canlet.2008.09.034

[41]

Barbero S "Stromal cell‐derived factor 1α stimulates human glioblastoma cell growth through the activation of both extracellular signal‐regulated kinases1/2 and Akt" Cancer Res (2003)

[42]

10.1016/j.cellsig.2005.03.022

[43]

10.1016/j.bbrc.2007.05.182

[44]

10.1016/j.regpep.2009.10.001

[45]

10.1074/jbc.m404097200

[46]

Tsuzuki Y "Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia inducible factor‐1α→ hypoxia response element → VEGF cascade differentially regulates vascular response and growth rate in tumours" Cancer Res (2000)

[47]

10.1158/0008-5472.can-03-2239

[48]

10.1023/b:agen.0000037332.66411.f0

[49]

10.1091/mbc.e04-05-0374

[50]

10.1016/j.cellsig.2006.12.014

Showing 50 of 54 references

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Details

Published: May 27, 2011
Vol/Issue: 224(3)
Pages: 344-354
License: View

Authors

Institute of Pathology and Southwest Cancer Centre Southwest Hospital, Third Military Medical University and Key Laboratory of Tumour Immunopathology, Ministry of Education of China Chongqing 400038 People's Republic of China

Harbin Medical University

Institute of Soil Fertilizer and Agricultural Water Saving, Xinjiang Academy of Agricultural Sciences, Urumqi 830091, China

R

Rong Zhang

Guangzhou University of Chinese Medicine

Y

You‐Hong Cui

Institute of Pathology and Southwest Cancer Centre Southwest Hospital, Third Military Medical University and Key Laboratory of Tumour Immunopathology, Ministry of Education of China Chongqing 400038 People's Republic of China

C

Cheng Qian

Ocean College, Zhejiang University , Zhoushan 316021, Zhejiang ,

Institute of Pathology and Southwest Cancer Centre Southwest Hospital, Third Military Medical University and Key Laboratory of Tumour Immunopathology, Ministry of Education of China Chongqing 400038 People's Republic of China

Cite This Article

Yi‐fang Ping, Xiao‐Hong Yao, Jian‐yong Jiang, et al. (2011). The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell‐mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling. The Journal of Pathology, 224(3), 344-354. https://doi.org/10.1002/path.2908

The chemokine CXCL12 and its receptor CXCR4 promote glioma stem cell‐mediated VEGF production and tumour angiogenesis via PI3K/AKT signalling

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