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CXCR4 expression mediates glioma cell
invasiveness
M Ehtesham1,2,3,
J A Winston1, P Kabos4
and R C Thompson1,3
1Department
of Neurological Surgery, Vanderbilt University Medical Center,
Nashville, TN, USA. 2Department of
Cancer Biology, Vanderbilt University Medical Center, Nashville, TN,
USA. 3Vanderbilt Ingram Cancer Center,
Vanderbilt University Medical Center, Nashville, TN, USA. 4Department
of Medicine, University of Southern California, Los Angeles, CA, USA.
Correspondence: Dr M Ehtesham, T-4224, Medical Center North,
Vanderbilt University Medical Center, Nashville, TN 37232-2380, USA.
E-mail: moneeb.ehtesham@vanderbilt.edu.
Received 18 December 2004; Revised 27 October 2005;
Accepted 4 November 2005; Published online 9 January 2006.
Glioblastoma multiforme is a highly
invasive tumor bearing a dismal prognosis.
Experimental strategies that focus on the specific biological cues
governing the invasive capacity of these tumors may hold significant
therapeutic promise.
In this context, we describe the in vitro
and in vivo association of the cell surface
chemokine receptor, CXCR4, with the development of an invasive
phenotype in malignant glioblastoma.
We demonstrate that invasive populations of glioma cells overexpress
CXCR4 at the message and protein levels, and that this expression
ranges from 25- to 89-fold higher than that found in noninvasive tumor
cells.
Furthermore, neutralization of CXCR4 significantly impairs the in
vitro invasive capacity of malignant glial cells.
In addition, glioma cells secrete CXCL12 and demonstrate robust
invasive capacity toward a CXCL12 gradient in
vitro.
These findings underscore the importance of CXCR4 as a potential
therapeutic target for the treatment of invasive glioblastoma.
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