CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells.
OBJECTIVE
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.
Sehgal
A
A
Pacific Northwest Cancer Foundation, Northwest Hospital, Seattle, Washington 98125, USA. asehgal@nwbio.org
Keener
C
C
Boynton
A L
AL
Warrick
J
J
Murphy
G P
GP
D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction / Q000379:methods; D012194:RNA-Directed DNA Polymerase; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D017931:DNA Primers; D019718:Receptors, CXCR4; D012194:RNA-Directed DNA Polymerase