MCP-1 Targeting: Shutting off an Engine for Tumor Development

Overview

Journal Oncol Lett

Specialty Oncology

Date 2021 Dec 6

PMID 34868363

Citations 14

Authors

Liang Wang

Jinxin Lan

Jiaping Tang

Na Luo

Affiliations

Soon will be listed here.

Abstract

A large amount of research has proven that monocyte chemotactic protein-1 (MCP-1) is associated with different types of disease, including autoimmune, metabolic and cardiovascular diseases. In addition, several studies have found that MCP-1 is associated with tumor development. MCP-1 expression level in the tumor microenvironment is associated with tumor development, including in tumor invasion and metastasis, angiogenesis, and immune cell infiltration. However, the precise mechanism involved is currently being investigated. MCP-1 exerts its effects mainly via the MCP-1/C-C motif chemokine receptor 2 axis and leads to the activation of classical signaling pathways, such as PI3K/Akt/mTOR, ERK/GSK-3β/Snail, c-Raf/MEK/ERK and MAPK in different cells. The specific mechanism is still under debate; however, target therapy utilizing MCP-1 as a neutralizing antibody has been found to have a detrimental effect on tumor development. The aim of the present review was to examine the effect of MCP-1 on tumor development from several aspects, including its structure, its involvement in signaling pathways, the participating cells, and the therapeutic agents targeting MCP-1. The improved understanding into the structure of MCP-1 and the mechanism of action may facilitate new and practical therapeutic agents to achieve maximum performance in the treatment of patients with cancer.

Citing Articles

Combinatory actions of cytokines induce M2-like macrophages in anaplastic thyroid cancer.

Kimura T, Kruhlak M, Zhao L, Hwang E, Fozzatti L, Cheng S Am J Cancer Res. 2025; 14(12):5812-5825.

PMID: 39803637 PMC: 11711523. DOI: 10.62347/QUWQ3794.

Association of Sympathovagal Imbalance with Increased Inflammation and Impaired Adaptive Immunity in Bladder Cancer Patients.

Mikolaskova I, Zvarik M, Szaboova K, Tibenska E, Durmanova V, Suchankova M Int J Mol Sci. 2024; 25(23).

PMID: 39684475 PMC: 11641687. DOI: 10.3390/ijms252312765.

Correlation of Cytokine Profiles with Prostate-Specific Antigen and Disease Grade in Prostate Cancer.

Sulic J, Marijanovic I, Kraljevic M, Sucur A, Kelava T, Mikulic I Med Sci Monit Basic Res. 2024; 30:e946776.

PMID: 39568188 PMC: 11600637. DOI: 10.12659/MSMBR.946776.

Discovery of a 6-Aminobenzo[]thiophene 1,1-Dioxide Derivative (K2071) with a Signal Transducer and Activator of Transcription 3 Inhibitory, Antimitotic, and Senotherapeutic Activities.

Oleksak P, Rysanek D, Vancurova M, Vasicova P, Urbancokova A, Novak J ACS Pharmacol Transl Sci. 2024; 7(9):2755-2783.

PMID: 39296273 PMC: 11406704. DOI: 10.1021/acsptsci.4c00190.

Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

Herrera-Martinez A, Romo A, Leon-Idougourram S, Munoz-Jimenez C, Rodriguez-Alonso R, Manzano Garcia G Int J Mol Sci. 2024; 25(11).

PMID: 38892006 PMC: 11171732. DOI: 10.3390/ijms25115821.

References

Mohamed H, El-Ghonaimy E, El-Shinawi M, Hosney M, Gotte M, Woodward W . IL-8 and MCP-1/CCL2 regulate proteolytic activity in triple negative inflammatory breast cancer a mechanism that might be modulated by Src and Erk1/2. Toxicol Appl Pharmacol. 2020; 401:115092. DOI: 10.1016/j.taap.2020.115092. View

Tang C, Tsai C . CCL2 increases MMP-9 expression and cell motility in human chondrosarcoma cells via the Ras/Raf/MEK/ERK/NF-κB signaling pathway. Biochem Pharmacol. 2011; 83(3):335-44. DOI: 10.1016/j.bcp.2011.11.013. View

Yoshimura T, Yuhki N, Moore S, Appella E, Lerman M, Leonard E . Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989; 244(2):487-93. DOI: 10.1016/0014-5793(89)80590-3. View

Schweickart V, Epp A, Raport C, Gray P . CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. J Biol Chem. 2000; 275(13):9550-6. DOI: 10.1074/jbc.275.13.9550. View

Loberg R, Ying C, Craig M, Yan L, Snyder L, Pienta K . CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration. Neoplasia. 2007; 9(7):556-62. PMC: 1939930. DOI: 10.1593/neo.07307. View

Sodhi A, Biswas S . Monocyte chemoattractant protein-1-induced activation of p42/44 MAPK and c-Jun in murine peritoneal macrophages: a potential pathway for macrophage activation. J Interferon Cytokine Res. 2002; 22(5):517-26. DOI: 10.1089/10799900252981990. View

Castineiras-Landeira M, Rodino-Janeiro B, Paradela-Dobarro B, Batista-Oliveira A, Raposeiras-Roubin S, Gonzalez-Peteiro M . Change of concept about the regulation of angiotensin II-induced monocyte chemoattractant protein-1 production in human endothelial cells. Vascul Pharmacol. 2016; 80:20-34. DOI: 10.1016/j.vph.2015.12.003. View

Cranford T, Velazquez K, Enos R, Bader J, Carson M, Chatzistamou I . Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model. Cancer Biol Ther. 2017; 18(2):85-93. PMC: 5362997. DOI: 10.1080/15384047.2016.1276135. View

Wichmann G, Korner C, Boehm A, Mozet C, Dietz A . Stimulation by Monocyte Chemoattractant Protein-1 Modulates the Ex-vivo Colony Formation by Head and Neck Squamous Cell Carcinoma Cells. Anticancer Res. 2015; 35(7):3917-24. View

10.

Nakatsumi H, Matsumoto M, Nakayama K . Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages. Cell Rep. 2017; 21(9):2471-2486. DOI: 10.1016/j.celrep.2017.11.014. View

11.

Sun C, Li X, Guo E, Li N, Zhou B, Lu H . MCP-1/CCR-2 axis in adipocytes and cancer cell respectively facilitates ovarian cancer peritoneal metastasis. Oncogene. 2019; 39(8):1681-1695. PMC: 8290627. DOI: 10.1038/s41388-019-1090-1. View

12.

Fujimoto H, Sangai T, Ishii G, Ikehara A, Nagashima T, Miyazaki M . Stromal MCP-1 in mammary tumors induces tumor-associated macrophage infiltration and contributes to tumor progression. Int J Cancer. 2009; 125(6):1276-84. DOI: 10.1002/ijc.24378. View

13.

Liu W, Wang L, Zhang J, Qiao L, Liu Y, Yang X . Purification of recombinant human chemokine CCL2 in and its function in ovarian cancer. 3 Biotech. 2021; 11(1):8. PMC: 7778648. DOI: 10.1007/s13205-020-02571-0. View

14.

Deng W, Gu X, Lu Y, Gu C, Zheng Y, Zhang Z . Down-modulation of TNFSF15 in ovarian cancer by VEGF and MCP-1 is a pre-requisite for tumor neovascularization. Angiogenesis. 2012; 15(1):71-85. DOI: 10.1007/s10456-011-9244-y. View

15.

Mehrabian M, Sparkes R, Mohandas T, Fogelman A, Lusis A . Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1. Genomics. 1991; 9(1):200-3. DOI: 10.1016/0888-7543(91)90239-b. View

16.

Salcedo R, Ponce M, Young H, Wasserman K, Ward J, Kleinman H . Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000; 96(1):34-40. View

17.

Zhang J, Lu Y, Pienta K . Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst. 2010; 102(8):522-8. PMC: 2857800. DOI: 10.1093/jnci/djq044. View

18.

Roy R, Wuthrich M, Klein B . Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent innate allergic inflammation in the lung. J Immunol. 2012; 189(5):2545-52. PMC: 3424300. DOI: 10.4049/jimmunol.1200689. View

19.

Bonini J, Martin S, Dralyuk F, Roe M, Philipson L, Steiner D . Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3. DNA Cell Biol. 1997; 16(10):1249-56. DOI: 10.1089/dna.1997.16.1249. View

20.

Yang X, Lin Y, Shi Y, Li B, Liu W, Yin W . FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer Res. 2016; 76(14):4124-35. DOI: 10.1158/0008-5472.CAN-15-2973. View