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CCL2/CCR2 signaling pathway in tumorigenesis and metastasis (Review)
Ya Zhang1,2, Bin Fan1,2, Hang Yang2
1Bone and Soft Tissue Tumors Research Centre of Yunnan Province, Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, Yunnan 650118, P.R. China.
Abstract:
C-C motif chemokine ligand 2 (CCL2) is associated with tumorigenesis and cancer progression. C-C motif chemokine receptor 2 (CCR2) is the main receptor of CCL2. The present review aimed to summarize the role of the CCL2/CCR2 signaling axis in tumorigenesis and metastasis. The CCL2/CCR2 signaling axis exerts antitumor activities by activating the immune response and immunosurveillance, recruiting neutrophils to destroy cancer cells, inducing tumor-infiltrating lymphocytes to infiltrate tumor tissue, and interfering with the function of T lymphocytes and dendritic cells. In addition, it promotes tumor progression by enhancing cell proliferation, migration and invasion, inducing epithelial-mesenchymal transition, stimulating the production of vascular endothelial growth factor and tumor angiogenesis, recruiting tumor-related cells to the tumor niche and remodeling the tumor microenvironment to render it immunosuppressive. The dual effect of the CCL2/CCR2 signaling axis depends on the specific conditions and stage of tumor metastasis.
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