CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression.
Chemokines, small pro-inflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 (also called stromal-derived factor-1) is an important α-chemokine that binds primarily to its cognate receptor CXCR4 and thus regulates the trafficking of normal and malignant cells. For many years, it was believed that CXCR4 was the only receptor for CXCL12. Yet, recent work has demonstrated that CXCL12 also binds to another seven-transmembrane span receptor called CXCR7. Our group and others have established critical roles for CXCR4 and CXCR7 on mediating tumor metastasis in several types of cancers, in addition to their contributions as biomarkers of tumor behavior as well as potential therapeutic targets. Here, we review the current concepts regarding the role of CXCL12 / CXCR4 / CXCR7 axis activation, which regulates the pattern of tumor growth and metastatic spread to organs expressing high levels of CXCL12 to develop secondary tumors. We also summarize recent therapeutic approaches to target these receptors and/or their ligands.
Sun
Xueqing
X
Department of Biochemistry and Molecular & Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Cheng
Guangcun
G
Hao
Mingang
M
Zheng
Jianghua
J
Zhou
Xiaoming
X
Zhang
Jian
J
Taichman
Russell S
RS
Pienta
Kenneth J
KJ
Wang
Jianhua
J
D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*
C501896:ACKR3 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4