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CCL18 in the Progression of Cancer.

ABSTRACT: A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are tumor-associated macrophages (TAMs). These cells secrete many chemokines into the tumor microenvironment, including especially a large amount of CCL18. This chemokine is a marker of the M2 macrophage subset; this is the reason why an increase in the production of CCL18 is associated with the immunosuppressive nature of the tumor microenvironment and an important element of cancer immune evasion. Consequently, elevated levels of CCL18 in the serum and the tumor are connected with a worse prognosis for the patient. This paper shows the importance of CCL18 in neoplastic processes. It includes a description of the signal transduction from PITPNM3 in CCL18-dependent migration, invasion, and epithelial-to-mesenchymal transition (EMT) cancer cells. The importance of CCL18 in angiogenesis has also been described. The paper also describes the effect of CCL18 on the recruitment to the cancer niche and the functioning of cells such as TAMs, regulatory T cells (Treg), cancer-associated fibroblasts (CAFs) and tumor-associated dendritic cells (TADCs). The last part of the paper describes the possibility of using CCL18 as a therapeutic target during anti-cancer therapy.

SUBMITTER: Korbecki J

PROVIDER: S-EPMC7663205 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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CCL18 in the Progression of Cancer.

Korbecki Jan J Olbromski Mateusz M Dzięgiel Piotr P

International journal of molecular sciences 20201026 21

A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are tumor-associated macrophages (TAMs). These cells secrete many chemokines into the tumor microenvironment, including especially a large amount of CCL18. This chemokine is a marker of the M2 macrophage subset; this is the reason why an increase in the production of CCL18 is associated with the immunosuppressive nature of the tumor microenvi ...[more]

PMID: 33114763

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Project description:BackgroundTumor-associated macrophages can promote breast cancer metastasis by secreting cytokines and growth factors. Interleukin (IL)-32θ, a newly identified IL-32 isoform, was previously shown to down-regulate various proinflammatory factors of macrophages. Here, we report the presence of IL-32θ in breast cancer tissues and evaluate its effects on macrophage-regulated breast cancer metastasis.MethodsRT-qPCR was used to analyze the mRNA expression of IL-32θ, Chemokine (C-C motif) ligand 18 (CCL18) in breast cancer tissues. In vitro cell-based experiments using IL-32θ-expressing MDA-MB-231 cells were conducted to examine the effects of IL-32θ on metastasis and its molecular signaling. In vivo xenograft, immunohistochemistry, and optical imaging models were generated to support in vitro and clinical findings.ResultsThe clinical data displayed opposite expression patterns of CCL18 and IL-32θ mRNA in macrophage-infiltrated breast tumor tissues compared with those in the other tissues tested. In MDA-MB-231 cells, IL-32θ overexpression attenuated migration, invasion, tumor-promoting factors, and increased epithelial markers levels upon treatment with conditioned media from THP-1-derived macrophages. Additionally, IL-32θ expression in a xenograft model led to a remarkable decrease in tumor size and macrophage-stimulated tumor promotion. This inhibition was mediated through a direct interaction with protein kinase C-δ (PKCδ), subsequently eliminating the downstream factors STAT3 and NF-κB. Blocking CCL18 during co-culture of macrophages and breast cancer cells reduced the levels of breast cancer progression-related factors and PKCδ downstream signaling suggesting CCL18 as the main macrophage-secreted factors triggering the signaling pathway inhibited by IL-32θ.ConclusionsOur findings demonstrate a novel role of IL-32θ as an intracellular modulator to suppress macrophage-promoted breast cancer progression by targeting CCL18-dependent signaling.

Dataset Information

CCL18 in the Progression of Cancer.

Publications

CCL18 in the Progression of Cancer.

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