Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo.
The chemokine CXCL12/SDF-1 and its receptor CXCR4 have been implicated in invasion, survival and proliferation of carcinoma cells. Recently, CXCR7 was identified as a second receptor for CXCL12. We observed that CXCL12 promoted proliferation of CT26 colon and KEP1 mammary carcinoma cells, and this was blocked when CXCR7 was downregulated by 'intrakines' or RNAi, but not by CXCR4 inhibitors. The K1R mutant of CXCL12, which acts as a CXCR4 antagonist, also promoted proliferation through CXCR7 and is therefore a selective CXCR7 agonist. The effect of CXCR7 was not due to reduced apoptosis, and CXCR7 mediated chemotaxis of the carcinoma cells towards CXCL12. These results differ from those in a previous report on other carcinoma cells. We conclude that CXCL12 can be a potent growth factor for carcinoma cells by acting on CXCR7. Nevertheless, we observed no effect of complete and stable CXCR7 suppression on the growth of s.c. tumours or lung metastases of KEP1 and CT26 cells. A CXCR7 inhibitor has been reported to reduce growth of other tumours. Our results indicate that this inhibitor may not be applicable to therapy of all carcinomas.
Division of Cell Biology, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066CX Amsterdam, The Netherlands.
J
J
Meijer
J
J
Ogink
E
E
Roos
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000502:physiology; D002633:Chemotaxis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology*; D034622:RNA Interference; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR