Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo
Open Access
- 14 October 2008
- journal article
- retraction
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 99 (9), 1493-1501
- https://doi.org/10.1038/sj.bjc.6604727
Abstract
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.Keywords
This publication has 28 references indexed in Scilit:
- The Chemokine Receptor CXCR6 and Its Ligand CXCL16 Are Expressed in Carcinomas and Inhibit ProliferationCancer Research, 2008
- Regulation of the Chemokine Receptor CXCR4 by HypoxiaThe Journal of Experimental Medicine, 2003
- A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumorsProceedings of the National Academy of Sciences, 2003
- Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHLNature, 2003
- The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases.2003
- A multigenic program mediating breast cancer metastasis to boneCancer Cell, 2003
- Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt.2003
- Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridomaJCI Insight, 2001
- Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140Bioorganic & Medicinal Chemistry Letters, 2001
- Involvement of chemokine receptors in breast cancer metastasisNature, 2001