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Discover Oncology
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Open Access 01-12-2024 | Metastasis | Research

The effect and mechanism of IL-37d on neutrophil recruitment in the early stage of tumor metastasis in the lungs

Authors: Yetong Guan, Chang Gao, Yan Guo, Meifang Wang, Lining Zhang

Published in: Discover Oncology | Issue 1/2024

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Abstract

Background

Chronic inflammation plays a pivotal role in cancer progression, with tumor-associated neutrophils (TANs) actively shaping the pre-metastatic niche. Interleukin-37 (IL-37), a known immunosuppressive cytokine, is implicated in this regulation, although its precise function remains underexplored.Therefore, this study seeks to further elucidate the inhibitory effect of IL-37d on neutrophil recruitment within the pre-metastatic lung microenvironment and its underlying mechanisms, thereby providing a theoretical foundation for clinical interventions in the early stages of cancer progression.

Methods

This study investigates the impact of IL-37d on tumor growth, metastasis, and survival in a murine model, with a focus on the molecular mechanisms involved. Specifically, we explored IL-37d's ability to inhibit toll-like receptor 3 (TLR3) activation in lung epithelial cells, reduce calcium-binding proteins S100A8/A9 (S100a8/9) expression, and suppress matrix metalloproteinase 9 (MMP9) activity. We also examined IL-37d’s effect on neutrophil migration from the bone marrow to the lungs during early metastasis.

Results

IL-37d treatment significantly reduced lung metastasis and extended survival in mice. Mechanistically, IL-37d inhibited TLR3 activation, downregulated S100a8/9 expression, and reduced MMP9 activity, thereby impairing the migration of bone marrow-derived neutrophils to the lungs. This led to decreased neutrophil infiltration and a disruption of the pre-metastatic niche formation.

Conclusion

Our study represents the first investigation into the role of IL-37d in inhibiting tumor metastasis during the early stages by suppressing S100A8/9 and MMP9 expression in lung tissue, thereby reducing neutrophil recruitment and spontaneous migration from the bone marrow.
Literature
1.
Liu Y, Cao X. Characteristics and significance of the pre-metastatic Niche. Cancer Cell. 2016;30(5):668–81.CrossRefPubMed
2.
3.
4.
5.
6.
Paget S. The distribution of secondary growths in cancer of the breast 1889 Cancer. Metastasis Rev. 1989;8(2):98–101.
7.
8.
刘洋 and 曹雪涛, 肿瘤转移前微环境的特征与作用. 中国肿瘤生物治疗杂志, 2017, 2017. 24(10): 1148–1150
9.
Comen EA. Tracking the seed and tending the soil: evolving concepts in metastatic breast cancer. Discov Med. 2012;14(75):97–104.PubMed
10.
Wu J, et al. Emerging nanomedicine-based therapeutics for hematogenous metastatic cascade inhibition: Interfering with the crosstalk between “seed and soil.” Acta Pharm Sin B. 2021;11(8):2286–305.CrossRefPubMedPubMedCentral
11.
Zhongyu X, et al. Review of pre-metastatic niches induced by osteosarcoma-derived extracellular vesicles in lung metastasis: A potential opportunity for diagnosis and intervention. Biomed Pharmacother. 2024;178: 117203.CrossRefPubMed
12.
Surendran V, et al. A novel tumor-immune microenvironment (TIME)-on-Chip mimics three dimensional neutrophil-tumor dynamics and neutrophil extracellular traps (NETs)-mediated collective tumor invasion. Biofabrication. 2021;13(3):035029.CrossRef
13.
Bergfeld SA, DeClerck YA. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev. 2010;29(2):249–61.CrossRefPubMed
14.
15.
Liu Y, Liu L. The pro-tumor effect and the anti-tumor effect of neutrophils extracellular traps. Biosci Trends. 2020;13(6):469–75.CrossRefPubMed
16.
17.
Liu Y, et al. Tumor exosomal RNAs promote lung pre-metastatic niche formation by activating alveolar Epithelial TLR3 to recruit neutrophils. Cancer Cell. 2016;30(2):243–56.CrossRefPubMed
18.
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016;16(7):431–46.CrossRefPubMed
19.
20.
21.
Bai J, et al. IL-37 as a potential biotherapeutics of inflammatory diseases. Curr Drug Targets. 2020;21(9):855–63.CrossRefPubMed
22.
23.
Li S, et al. Extracellular forms of IL-37 inhibit innate inflammation in vitro and in vivo but require the IL-1 family decoy receptor IL-1R8. Proc Natl Acad Sci U S A. 2015;112(8):2497–502.CrossRefPubMedPubMedCentral
24.
Cavalli G, Dinarello CA. Suppression of inflammation and acquired immunity by IL-37. Immunol Rev. 2018;281(1):179–90.CrossRefPubMed
25.
26.
Li Y, et al. Intracellular mature IL-37 suppresses tumor metastasis via inhibiting Rac1 activation. Oncogene. 2018;37(8):1095–106.CrossRefPubMed
27.
28.
29.
Guo Y, et al. IL-37d enhances COP1-mediated C/EBPβ degradation to suppress spontaneous neutrophil migration and tumor progression. Cell Rep. 2024;43(2): 113787.CrossRefPubMed
30.
De Cicco P, Ercolano G, Ianaro A. The new era of cancer immunotherapy: targeting myeloid-derived suppressor cells to overcome immune evasion. Front Immunol. 2020;11:1680.CrossRefPubMedPubMedCentral
31.
C.M., G.C. Learners’ cognitive processing problems during comprehension as a basis for L2 listening research. System. 2023;119:103164.
32.
33.
34.
Li Y, et al. IL-37d negatively regulates NLRP3 transcription via receptor-mediated pathway and alleviates DSS-induced Colitis. Inflamm Bowel Dis. 2021;27(1):84–93.CrossRefPubMed
35.
Li C, et al. IL-37 isoform D acts as an inhibitor of soluble ST2 to boost type 2 immune homeostasis in white adipose tissue. Cell Death Discov. 2022;8(1):163.CrossRefPubMedPubMedCentral
36.
Chung YH, et al. Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis. Proc Natl Acad Sci U S A. 2023;120(43): e2221859120.CrossRefPubMedPubMedCentral
37.
38.
Rathinam R, Berrier A, Alahari SK. Role of Rho GTPases and their regulators in cancer progression. Front Biosci (Landmark Ed). 2011;16(7):2561–71.CrossRefPubMed
39.
Bagci H, et al. Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nat Cell Biol. 2020;22(1):120–34.CrossRefPubMed
Metadata
Title
The effect and mechanism of IL-37d on neutrophil recruitment in the early stage of tumor metastasis in the lungs
Authors
Yetong Guan
Chang Gao
Yan Guo
Meifang Wang
Lining Zhang
Publication date
01-12-2024
Publisher
Springer US
Keyword
Metastasis
Published in
Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-024-01608-7

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