CCL2 in the Tumor Microenvironment

The C-C motif chemokine ligand 2 (CCL2) is a crucial mediator of immune cell recruitment during microbial infections and tissue damage. CCL2 is also frequently overexpressed in cancer cells and other cells in the tumor microenvironment, and a large body of evidence indicates that high CCL2 levels are associated with more aggressive malignancies, a higher probability of metastasis, and poorer outcomes in a wide range of cancers. CCL2 plays a role in recruiting tumor-associated macrophages (TAMs), which adopt a pro-tumorigenic phenotype and support cancer cell survival, facilitate tumor cell invasion, and promote angiogenesis. CCL2 also has direct, TAM-independent effects on tumor cells and the tumor microenvironment, including recruitment of other myeloid subsets and non-myeloid cells, maintaining an immunosuppressive environment, stimulating tumor cell growth and motility, and promoting angiogenesis. CCL2 also plays important roles in the metastatic cascade, such as creating a pre-metastatic niche in distant organs and promoting tumor cell extravasation across endothelia. Due to its many roles in tumorigenesis and metastatic processes, the CCL2-CCR2 signaling axis is currently being pursued as a potential therapeutic target for cancer.