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Review
. 2020 Nov 9;21(21):8412.
doi: 10.3390/ijms21218412.

CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4

Jan Korbecki  1 , Klaudyna Kojder  2 , Donata Simińska  1 , Romuald Bohatyrewicz  2 , Izabela Gutowska  3 , Dariusz Chlubek  1 , Irena Baranowska-Bosiacka  1
Affiliations
Review

CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4

Jan Korbecki et al. Int J Mol Sci. .

Abstract

CC chemokines, a subfamily of 27 chemotactic cytokines, are a component of intercellular communication, which is crucial for the functioning of the tumor microenvironment. Although many individual chemokines have been well researched, there has been no comprehensive review presenting the role of all known human CC chemokines in the hallmarks of cancer, and this paper aims at filling this gap. The first part of this review discusses the importance of CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 in cancer. Here, we discuss the significance of CCL2 (MCP-1), CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL22, CCL23, CCL24, and CCL26. The presentation of each chemokine includes its physiological function and then the role in tumor, including proliferation, drug resistance, migration, invasion, and organ-specific metastasis of tumor cells, as well as the effects on angiogenesis and lymphangiogenesis. We also discuss the effects of each CC chemokine on the recruitment of cancer-associated cells to the tumor niche (eosinophils, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), regulatory T cells (Treg)). On the other hand, we also present the anti-cancer properties of CC chemokines, consisting in the recruitment of tumor-infiltrating lymphocytes (TIL).

Keywords: CC chemokine; MCP-1; angiogenesis; anti-cancer therapy; cancer; chemokine; lymphangiogenesis; organ-specific metastasis; tumor; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The role of CCL2 in caner. In a tumor, CCL2 is produced by tumor cells and by CAF and TAM. It activates its receptor, CCR2, on a tumor cell, which stimulates the proliferation of cancer cells and causes their migration and resistance to apoptosis. CCL2 also acts on non-cancer cells, e.g., activating CCR2 on vascular endothelial cells which results in angiogenesis. CCL2 causes the recruitment of MDSC, TAM, and Treg into the tumor niche but also induces the infiltration of the tumor by anti-cancer TIL.
Figure 2
Figure 2
The role of eotaxins in cancer. In a neoplastic cell there is an expression of CCL11 (eotaxin-1), CCL24 (eotaxin-2) and CCL26 (eotaxin-3). This increases the autocrine proliferation and causes the migration of cancer cells with CCR3 expression. Eotaxins also activate the CCR3 receptor on endothelial cells, which results in angiogenesis. Another effect of an increased expression of eotaxins in the tumor is the recruitment of cells into the tumor niche, in particular eosinophils, by all three eotaxins through the CCR3 receptor. MDSC are recruited into the tumor by CCL26 via CX3CR1.
Figure 3
Figure 3
The role of CCL17 and CCL22 in cancer. These two chemokines are produced by cancer cells, CAF, TAM, and TAN. They increase the proliferation of cancer cells and their migration and invasion. They also cause the recruitment of Treg and Th17. However, they can also cause infiltration of the tumor by TIL, which has an anti-cancer effect.
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References

    1. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 2000;100:57–70. doi: 10.1016/S0092-8674(00)81683-9. - DOI - PubMed
    1. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Liu Q., Yang C., Wang S., Shi D., Wei C., Song J., Lin X., Dou R., Bai J., Xiang Z., et al. Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression. Cell Commun. Signal. 2020;18:51. doi: 10.1186/s12964-020-00557-2. - DOI - PMC - PubMed
    1. Wang Z., Yang Y., Cui Y., Wang C., Lai Z., Li Y., Zhang W., Mustonen H., Puolakkainen P., Ye Y., et al. Tumor-associated macrophages regulate gastric cancer cell invasion and metastasis through TGFβ2/NF-κB/Kindlin-2 axis. Chin. J. Cancer Res. 2020;32:72–88. doi: 10.21147/j.issn.1000-9604.2020.01.09. - DOI - PMC - PubMed
    1. Wu H., Zhang X., Han D., Cao J., Tian J. Tumour-associated macrophages mediate the invasion and metastasis of bladder cancer cells through CXCL8. PeerJ. 2020;8:e8721. doi: 10.7717/peerj.8721. - DOI - PMC - PubMed

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