CXCL12 mediates apoptosis resistance in rat C6 glioma cells.
The chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) and its receptor             CXCR4 regulate migration and patterning processes during brain development, but             also contribute to proliferation and expansion of gliomas, the most malignant             brain tumors. Recently, a previous orphan-receptor CXCR7/RDC-1 was discovered             to 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 functional             relevance of CXCR7. Since the well-characterized rat C6 glioma cell line is commonly             used as a glioma model in vitro and in vivo, we investigated the expression, regulation             and function of CXCL12 and its receptors in these tumor cells. Whereas CXCL12             and CXCR7 were transcribed at notable levels, CXCR4 was quite low. By sublethal             doses of temozolomide, an alkylating drug commonly used in adjuvant glioma therapy,             transcription of CXCL12 and its receptors were significantly induced. Decreased             proliferation resulting from this sublethal treatment with temozolomide could             be completely restored to normal proliferation rates by simultaneous stimulation             with CXCL12. Similarly, CXCL12 protected C6 cells from apoptosis under treatment             with 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 these             mechanisms in vitro and in vivo.
Department of Anatomy, University of Kiel, D-24098 Kiel, Germany. k.hattermann@anat.uni-kiel.de
Kirsten
K
Hattermann
Rolf
R
Mentlein
Janka
J
Held-Feindt
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism* / Q000494:pharmacology; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D000077204:Temozolomide; D014158:Transcription, Genetic / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D003606:Dacarbazine; D000077204:Temozolomide