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Semin Cancer Biol. 2009 Apr;19(2):116-22. doi: 10.1016/j.semcancer.2008.10.001. Epub 2008 Oct 17.

Chemokine signaling in cancer: one hump or two?

Author information

1
Department of Pediatrics/Division of Pediatric Hematology and Oncology, Campus Box 8208, 660 South Euclid Avenue, Washington University School of Medicine, St Louis, MO 63110, USA. rubin j@kids.wustl.edu

Abstract

Chemokines and their receptors play essential roles in the development and function of multiple tissues. Chemokine expression, particularly CXCL12 and its receptor CXCR4, has prognostic significance in several cancers apparently due to chemokine mediated growth and metastatic spread. These observations provide the rationale for pursuing CXCR4 inhibition for cancer chemotherapy. However, the multiple homeostatic functions of CXCR4 may preclude global inhibition as a therapeutic strategy. Here I review CXCR4 signaling and how it might differ in normal and transformed cells with special emphasis on the role that altered CXCR4 counter-regulation might play in tumor biology. I propose that CXCR4 mediates unique signals in cancer cells as a consequence of abnormal counter-regulation and that this results in novel biological responses. The importance of testing this hypothesis lies in the possibility that targeting abnormal CXCR4 signaling might provide an anti-tumor effect without disturbing normal CXCR4 functions.

PMID:
18992347
PMCID:
PMC2694237
DOI:
10.1016/j.semcancer.2008.10.001
[Indexed for MEDLINE]
Free PMC Article

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