1. ¹Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
2. ²Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA
3. ³Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
4. 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.

Abstract

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.