CXCR-4, A CHEMOKINE RECEPTOR, IS OVEREXPRESSED IN AND REQUIRED FOR PROLIFERATION OF GLIOBLASTOMA TUMOR-CELLS

Background and Objectives: Using the technique of differential hybridi zation of Atlas(TM) Human cDNA expression arrays, we previously report ed the isolation of a G protein coupled receptor, CXCR-4, which is ove rexpressed in glioblastoma multiforme tumor tissue (GMTT) com pared to normal brain tissue (NBT). Methods: Using gene specific reverse trans criptase-polymerase chain reaction (RT-PCR) and in situ hybridization, we studied its expression in a variety of brain and breast tumor tiss ue samples. To demonstrate the requirement of CXCR-4 in glioblastoma c ell proliferation an antisense construct was overexpressed. Glioblasto ma cells were also treated with antibodies against CXCR-4 and its Liga nd, SDF beta-1. Results: Expression analysis indicated that CXCR-4 is overexpressed in 57% of the primary glioblastoma tissues and in 88% of the glioblastoma cell lines analyzed. Overexpression of CXCR-4 in gli oblastoma cell Lines enhanced their soft agar colony-forming capabilit y. Expression of antisense CXCR-4 in glioblastoma cell lines caused ne urite outgrowth and cellular differentiation. Treatment of glioblastom a cell lines with CXCR-4 and SDF beta-1 specific antibodies caused inh ibition of glioblastoma cell proliferation. Conclusions: On the basis of these results, we conclude that CXCR-4 gene is required for the pro liferation of human glioblastoma tumors. (C) 1998 Wiley-Liss, Inc.