CXCL12 mediates apoptosis resistance in rat C6 glioma cells

The chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) and its receptorCXCR4 regulate migration and patterning processes during brain development, butalso contribute to proliferation and expansion of gliomas, the most malignantbrain tumors. Recently, a previous orphan-receptor CXCR7/RDC-1 was discoveredto be a second receptor for CXCL12. CXCR7 has been detected in normal brain parenchyma,but in particular in human brain tumors. However, little is known about the functionalrelevance of CXCR7. Since the well-characterized rat C6 glioma cell line is commonlyused as a glioma model in vitro and in vivo, we investigated the expression, regulationand function of CXCL12 and its receptors in these tumor cells. Whereas CXCL12and CXCR7 were transcribed at notable levels, CXCR4 was quite low. By sublethaldoses of temozolomide, an alkylating drug commonly used in adjuvant glioma therapy,transcription of CXCL12 and its receptors were significantly induced. Decreasedproliferation resulting from this sublethal treatment with temozolomide couldbe completely restored to normal proliferation rates by simultaneous stimulationwith CXCL12. Similarly, CXCL12 protected C6 cells from apoptosis under treatmentwith higher temozolomide doses. Thus, the CXCL12-CXCR7 axis promotes glioma progression,and the rat C6 glioma cell line may be a useful model to further investigate thesemechanisms in vitro and in vivo.