Roles of CCL2-CCR2 Axis in the Tumor Microenvironment

Kadomoto, Suguru; Izumi, Kouji; Mizokami, Atsushi

doi:10.3390/ijms22168530

Cited by 73 publications

(63 citation statements)

References 122 publications

(158 reference statements)

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“…The results of migration assay experiments would confirm the anti-metastatic effects of vitamin D on thyroid cancer cell lines. However, the fact that basal cell migration occurred in a dose-dependent manner and was observed also for concentrations of vitamin D at which no inhibitory effect on chemokine secretion was demonstrated would support that the anti-migration effect of vitamin D would depend upon other mechanisms rather than by its ability to inhibit the secretion of CCL2 and CXCL8, chemokines that are known to be crucially involved in the metastatic process ( 27 , 32 – 34 ).…”

Section: Discussionmentioning

confidence: 94%

Vitamin D Reduces Thyroid Cancer Cells Migration Independently From the Modulation of CCL2 and CXCL8 Chemokines Secretion

et al. 2022

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BackgroundVitamin D3 is largely involved in the regulation of calcium homeostasis. More recently, it was demonstrated that vitamin D exerts several beneficial effects against cancer progression through several mechanisms, including the reduction of cancer cells proliferation and migration. CXCL8 and CCL2 are two chemokines secreted by thyroid tumor cells. In the thyroid tumor microenvironment, these chemokines exert several pro-tumorigenic effects including the one to increase the metastatic potential. The aim of the present study was to investigate if vitamin D could modulate both thyroid cancer cell migration and their ability to secrete CCL2 and CXCL8.MethodsTPC-1 (RET/PTC rearranged) and 8505C (BRAFV600e mutated) thyroid cancer cell lines were treated with increasing concentrations of 1,25-OH-vitamin D3 (0–1,000 nM). Cell viability was assessed by WST-1 assay, cell migration was evaluated by transwell–migration chamber system, and CCL2 and CXCL8 levels were measured in the cell culture supernatants by ELISA.ResultsVitamin D did not affect cell viability but reduced, in a dose-dependent and significant manner, thyroid cancer cell migration (ANOVAs p < 0.05 for both TPC-1 and 8505C). Vitamin D differently modulated the secretion of CCL2 and CXCL8, by significantly inhibiting the secretion of CCL2 in both thyroid cancer cell lines and inhibiting the secretion of CXCL8 only in TPC-1 (ANOVAs p < 0.05).ConclusionsVitamin D treatment of thyroid cancer cell lines reduces cell migration independently from the inhibition of the secretion of pro-tumorigenic chemokines. Future studies specifically designed at clarifying the pathways involved in the different inhibitory effects of vitamin D on CCL2 and CXCL8 in thyroid cancer cells appear worthwhile.

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Section: Discussionmentioning

confidence: 94%

Vitamin D Reduces Thyroid Cancer Cells Migration Independently From the Modulation of CCL2 and CXCL8 Chemokines Secretion

et al. 2022

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“…A recent study found the increase of CCL2 promoted carcinogenesis through esophageal mucosal inflammation [ 13 ]. Moreover, CCL2 could promote the survival and proliferation of THP-1, prostate cancer cell line PC3, renal cell carcinoma cell line 786-O and KAKI-1, and lung cancer cell line A549 [ 14 , 15 ]. The growth of cutaneous squamous cell carcinoma and non-small-cell lung cancer was promoted by tumor-cell-derived complement components C1r and C1s [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration

et al. 2022

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Glioblastoma multiforme (GBM) is a prevalent intracranial brain tumor associated with a high rate of recurrence and treatment difficulty. The prediction of novel molecular biomarkers through bioinformatics analysis may provide new clues into early detection and eventual treatment of GBM. Here, we used data from the GTEx and TCGA databases to identify 1923 differentially expressed genes (DEGs). GO and KEGG analyses indicated that DEGs were significantly enriched in immune response and coronavirus disease-COVID-19 pathways. Survival analyses revealed a significant correlation between high expression of C1R, CCL2, and TNFRSF1A in the coronavirus disease-COVID-19 pathway and the poor survival in GBM patients. Cell experiments indicated that the mRNA expression levels of C1R, CCL2, and TNFRSF1A in GBM cells were very high. Immune infiltration analysis revealed a significant difference in the proportion of immune cells in tumor and normal tissue, and the expression levels of C1R, CCL2, and TNFRSF1A were associated with immune cell infiltration of GBM. Additionally, the protein-protein interaction networks of C1R, CCL2, and TNFRSF1A involved a total of 65 nodes and 615 edges. These results suggest that C1R, CCL2, and TNFRSF1A may be used as molecular biomarkers of prognosis and immune infiltration in GBM patients in the future.

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“…In addition, various stromal cells in the TME, including endothelial cells, DCs, fibroblasts, and adipocytes, are capable of producing CCL2 to promote tumor growth and progression. 90 , 91 , 92 CCL2 was the first CC chemokine to be identified and fully studied and has a high affinity for its receptor, CCR2. It has been revealed that CCR2 is widely expressed in a broad range of cell types, including monocytes, 93 endothelial cells, 94 DCs, 95 and various cancer cells and the upregulation of CCR2 is related to advanced cancer, metastasis, and relapse.…”

Section: Different Chemokine Axesmentioning

confidence: 99%

“… 96 After reaching a new organ and/or tissue, residual circulating tumor cells are able to successfully colonize and continue to grow through interactions with various components within the TME. 91 It has been suggested that CCL2 might act as an autocrine or paracrine chemokine to promote the growth of tumor cells, which can be partially abolished by CCR2 antagonists or PI3K inhibitors. 115 CCL2 can promote drug resistance in gastric cancer cells by inhibiting autophagy, and either knockdown of CCL2 or induction of autophagy successfully reversed drug resistance in tumor cells.…”

Section: Different Chemokine Axesmentioning

confidence: 99%

Role of chemokine systems in cancer and inflammatory diseases

Zhao

2022

MedComm

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Chemokines are a large family of small secreted proteins that have fundamental roles in organ development, normal physiology, and immune responses upon binding to their corresponding receptors. The primary functions of chemokines are to coordinate and recruit immune cells to and from tissues and to participate in regulating interactions between immune cells. In addition to the generally recognized antimicrobial immunity, the chemokine/chemokine receptor axis also exerts a tumorigenic function in many different cancer models and is involved in the formation of immunosuppressive and protective tumor microenvironment (TME), making them potential prognostic markers for various hematologic and solid tumors. In fact, apart from its vital role in tumors, almost all inflammatory diseases involve chemokines and their receptors in one way or another. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases. Here, we summarize recent advances of chemokine systems in protumor and antitumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. In this review, we also emphatically highlight the complexity of the chemokine system and explore its potential to guide the treatment of cancer and inflammatory diseases.

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Roles of CCL2-CCR2 Axis in the Tumor Microenvironment

Cited by 73 publications

References 122 publications

Vitamin D Reduces Thyroid Cancer Cells Migration Independently From the Modulation of CCL2 and CXCL8 Chemokines Secretion

Vitamin D Reduces Thyroid Cancer Cells Migration Independently From the Modulation of CCL2 and CXCL8 Chemokines Secretion

C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and Immune Infiltration

Role of chemokine systems in cancer and inflammatory diseases

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