Background and objectives: Using the technique of differential hybridization of Atlas Human cDNA expression arrays, we previously reported the isolation of a G protein coupled receptor, CXCR-4, which is overexpressed in glioblastoma multiforme tumor tissue (GMTT) compared to normal brain tissue (NBT).

Methods: Using gene specific reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization, we studied its expression in a variety of brain and breast tumor tissue samples. To demonstrate the requirement of CXCR-4 in glioblastoma cell proliferation an antisense construct was overexpressed. Glioblastoma cells were also treated with antibodies against CXCR-4 and its ligand, SDFbeta-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 glioblastoma cell lines enhanced their soft agar colony-forming capability. Expression of anti-sense CXCR-4 in glioblastoma cell lines caused neurite outgrowth and cellular differentiation. Treatment of glioblastoma cell lines with CXCR-4 and SDFbeta-1 specific antibodies caused inhibition of glioblastoma cell proliferation.

Conclusions: On the basis of these results, we conclude that CXCR-4 gene is required for the proliferation of human glioblastoma tumors.