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CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks

Abstract

Increasing evidence indicates that the tumor microenvironment has critical roles in all aspects of cancer biology, including growth, angiogenesis, metastasis and progression. Although chemokines and their receptors were originally identified as mediators of inflammatory diseases, it is being increasingly recognized that they serve as critical communication bridges between tumor cells and stromal cells to create a permissive microenvironment for tumor growth and metastasis. Thus, an important therapeutic strategy for cancer is to break this communication channel and isolate tumor cells for long-term elimination. Cytokine CXCL12 (also known as stromal-derived factor 1α) and its receptor CXCR4 represent the most promising actionable targets for this strategy. Both are overexpressed in various cancer types, and this aberrant expression strongly promotes proliferation, migration and invasion through multiple signal pathways. Several molecules that target CXCL12 or CXCR4 have been developed to interfere with tumor growth and metastasis. In this article, we review our current understanding of the CXCL12/CXCR4 axis in cancer tumorigenesis and progression and discuss its therapeutic implications.

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Acknowledgements

We thank Ann Sutton from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for editing this manuscript. This work was partially supported by funds from the Tianjin Municipal Science and Technology Commission International Cooperation Foundation (No. 15RCGFSY00108), the Natural Science Fund of Tianjin Municipal Science and Technology Commission (No. 12JCYBJC17900), and the Tianjin Medical University Science Foundation (No. 2014KYQ03).

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Guo, F., Wang, Y., Liu, J. et al. CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene 35, 816–826 (2016). https://doi.org/10.1038/onc.2015.139

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