Molecular characterization of CXCR-4: a potential brain tumor-associated gene.

BACKGROUND AND

OBJECTIVES

We have previously reported the isolation of a G protein-coupled receptor, CXCR-4, that is overexpressed in glioblastoma multiforme tumor tissue (GMTT), as compared to normal brain tissue (NBT).

METHODS

Gene-specific RT-PCR, Northern blotting, and in situ hybridization techniques were used to study its expression in a variety of normal tissues, tumor tissues, and cell lines, as well as during development. Antisense CXCR-4 was overexpressed in glioblastoma cells to study its effect on cell proliferation.

RESULTS

Gene-specific RT-PCR analysis indicated that the CXCR-4 gene is overexpressed in several malignant glioma tissues, breast tumor tissues and cell lines. Northern blot analysis indicated that CXCR-4 is expressed at high levels in certain leukemias, uterine cancer, and Burkitt's lymphoma cell line. The occipital and temporal lobe showed high levels of CXCR4 in normal human brain. The CXCR-4 gene was expressed in all organs in the early stages of development (days 8-10). In adult mouse, CXCR-4 is expressed only in brain, spinal cord, bone marrow, and pituitary gland. Antisense CXCR-4 overexpression in glioblastoma cells caused inhibition of cell proliferation and induction of cellular differentiation in vitro. This suggests that CXCR-4 expression may play an important role during embryonic development and also in the genesis of human gliomas.

CONCLUSIONS

On the basis of CXCR4 expression data and antisense overexpression data, we conclude that CXCR-4 plays an important role in the tumorigenic properties of brain, breast, and other tumor types. On the basis of its unique expression during mouse development, we conclude that it may play an important role in the normal functioning of brain, spinal cord, and bone marrow during development.