Targeting the CCL2-CCR2 signaling axis in cancer metastasis

// Su Yin Lim 1 , Arseniy E. Yuzhalin 1 , Alex N. Gordon-Weeks 1 and Ruth J. Muschel 1 1 CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom Correspondence to: Su Yin Lim, email: // Keywords : chemokines, cancer metastasis, cancer therapy, clinical trials Received : October 26, 2015 Accepted : January 31, 2016 Published : February 14, 2016 Abstract The CCL2-CCR2 signaling axis has generated increasing interest in recent years due to its association with the progression of cancer. Although first described as a chemotactic molecule with physiological roles in regulating inflammation, recent studies have revealed a pro-tumorigenic function for CCL2 in favoring cancer development and subsequent metastasis. CCL2 binds the cognate receptor CCR2, and together this signaling pair has been shown to have multiple pro-tumorigenic roles, from mediating tumor growth and angiogenesis to recruiting and usurping host stromal cells to support tumor progression. The importance of CCL2-CCR2 signaling has been further championed by the establishment of clinical trials targeting this signaling pair in solid and metastatic cancers. Here we review the roles of CCL2-CCR2 signaling in the development and progression of cancer metastasis. We further evaluate the outcome of several clinical trials targeting either CCL2 or CCR2, and discuss the prospects and challenges of manipulating CCL2-CCR2 interaction as a potential approach for combating metastatic disease.