Is the C-C Motif Ligand 2–C-C Chemokine Receptor 2 Axis a Promising Target for Cancer Therapy and Diagnosis?

Iwamoto, Hiroaki; Izumi, Kouji; Mizokami, Atsushi

doi:10.3390/ijms21239328

Cited by 29 publications

(23 citation statements)

References 107 publications

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“…Several studies have been conducted on the CCL2-CCR2 axis, and it has been pointed out that it functions as a major chemokine in inflammatory diseases and malignant tumors [20,21]. The CCL2-CCR2 axis exerts various functions in the process of malignant tumor growth, infiltration, and metastasis, and is involved in the progression of several malignant tumors [71].…”

Section: Relationship Between Malignant Tumors and Ccl2-ccr2 Axismentioning

confidence: 99%

Roles of CCL2-CCR2 Axis in the Tumor Microenvironment

Kadomoto

Izumi

Mizokami

2021

IJMS

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Chemokines are a small family of cytokines that were first discovered as chemotactic factors in leukocytes during inflammation, and reports on the relationship between chemokines and cancer progression have recently been increasing. The CCL2-CCR2 axis is one of the major chemokine signaling pathways, and has various functions in tumor progression, such as increasing tumor cell proliferation and invasiveness, and creating a tumor microenvironment through increased angiogenesis and recruitment of immunosuppressive cells. This review discusses the roles of the CCL2-CCR2 axis and the tumor microenvironment in cancer progression and their future roles in cancer therapy.

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Section: Relationship Between Malignant Tumors and Ccl2-ccr2 Axismentioning

confidence: 99%

Roles of CCL2-CCR2 Axis in the Tumor Microenvironment

Kadomoto

Izumi

Mizokami

2021

IJMS

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“…Besides triggering immune cell trafficking into the sites of inflammation, the activation of the CCL2-CCR2 axis can promote both direct and indirect pro-tumorigenic effects, fostering tumor cell proliferation, stemness and survival, as well as neoangiogenesis, local invasiveness and metastasis [ 19 ]. Consistently, CCL2 is overexpressed by a variety of solid and hematologic neoplasms, particularly breast, prostate, gastric, colorectal, pancreatic cancers and non-Hodgkin lymphomas [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of the rs1024611 Polymorphism of CCL2 on the Pathophysiology and Outcome of Primary Myelofibrosis

Masselli

Carubbi

Pozzi

et al. 2021

Cancers

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Single nucleotide polymorphisms (SNPs) can modify the individual pro-inflammatory background and may therefore have relevant implications in the MPN setting, typified by aberrant cytokine production. In a cohort of 773 primary myelofibrosis (PMF), we determined the contribution of the rs1024611 SNP of CCL2—one of the most potent immunomodulatory chemokines—to the clinical and biological characteristics of the disease, demonstrating that male subjects carrying the homozygous genotype G/G had an increased risk of PMF and that, among PMF patients, the G/G genotype is an independent prognostic factor for reduced overall survival. Functional characterization of the SNP and the CCL2-CCR2 axis in PMF showed that i) homozygous PMF cells are the highest chemokine producers as compared to the other genotypes; ii) PMF CD34+ cells are a selective target of CCL2, since they uniquely express CCR2 (CCL2 receptor); iii) activation of the CCL2-CCR2 axis boosts pro-survival signals induced by driver mutations via Akt phosphorylation; iv) ruxolitinib effectively counteracts CCL2 production and down-regulates CCR2 expression in PMF cells. In conclusion, the identification of the role of the CCL2/CCR2 chemokine system in PMF adds a novel element to the pathophysiological picture of the disease, with clinical and therapeutic implications.

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“…Among the different cytokines, chemokines are leukocyte chemotactic factors of relatively small molecular weight, but they are also important in TME [ 88 ]. Inhibition of CCL2 is important because CCL2 produced by cancer cells recruits macrophages to the TME and directly increases the metastatic potential of cancer cells [ 89 , 90 ]. The regulation of chemokines in TME is important because TAMs also produce chemokines that act on cancer cells, immune cells, and stromal cells [ 91 , 92 ].…”

Section: Cancer and Macrophagesmentioning

confidence: 99%

Macrophage Polarity and Disease Control

Kadomoto

Izumi

Mizokami

2021

IJMS

Self Cite

165

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Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.

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Is the C-C Motif Ligand 2–C-C Chemokine Receptor 2 Axis a Promising Target for Cancer Therapy and Diagnosis?

Cited by 29 publications

References 107 publications

Roles of CCL2-CCR2 Axis in the Tumor Microenvironment

Roles of CCL2-CCR2 Axis in the Tumor Microenvironment

Impact of the rs1024611 Polymorphism of CCL2 on the Pathophysiology and Outcome of Primary Myelofibrosis

Macrophage Polarity and Disease Control

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