CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells

✍ Scribed by Sehgal, Anil; Keener, Cassie; Boynton, Alton L.; Warrick, Jami; Murphy, Gerald P.

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 148 KB
• Volume: 69
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/(sici)1096-9098(199810)69:2<99::aid-jso10>3.0.co;2-m

✦ Synopsis

Background and Objectives: Using the technique of differential hybridization of Atlas TM 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, SDF␤-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 antisense CXCR-4 in glioblastoma cell lines caused neurite outgrowth and cellular differentiation. Treatment of glioblastoma cell lines with CXCR-4 and SDF␤-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.