MicroRNA-200c Restoration Reveals a Cytokine Profile to Enhance M1 Macrophage Polarization in Breast Cancer

Overview

Journal NPJ Breast Cancer

Date 2021 May 28

PMID 34045467

Citations 16

Authors

Michelle M Williams

Jessica L Christenson

Kathleen I ONeill

Sabrina A Hafeez

Claire L Ihle

Nicole S Spoelstra

Jill E Slansky

Jennifer K Richer

Affiliations

Soon will be listed here.

Abstract

Many immune suppressive mechanisms utilized by triple negative breast cancer (TNBC) are regulated by oncogenic epithelial-to-mesenchymal transition (EMT). How TNBC EMT impacts innate immune cells is not fully understood. To determine how TNBC suppresses antitumor macrophages, we used microRNA-200c (miR-200c), a powerful repressor of EMT, to drive mesenchymal-like mouse mammary carcinoma and human TNBC cells toward a more epithelial state. MiR-200c restoration significantly decreased growth of mouse mammary carcinoma Met-1 cells in culture and in vivo. Cytokine profiling of Met-1 and human BT549 cells revealed that miR-200c upregulated cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), promoted M1 antitumor macrophage polarization. Cytokines upregulated by miR-200c correlated with an epithelial gene signature and M1 macrophage polarization in BC patients and predicted a more favorable overall survival for TNBC patients. Our findings demonstrate that immunogenic cytokines (e.g., GM-CSF) are suppressed in aggressive TNBC, warranting further investigation of cytokine-based therapies to limit disease recurrence.

Citing Articles

Macrophage polarization in rheumatoid arthritis: signaling pathways, metabolic reprogramming, and crosstalk with synovial fibroblasts.

Zheng Y, Wei K, Jiang P, Zhao J, Shan Y, Shi Y Front Immunol. 2024; 15:1394108.

PMID: 38799455 PMC: 11116671. DOI: 10.3389/fimmu.2024.1394108.

The potential role of miRNA in regulating macrophage polarization.

Khayati S, Dehnavi S, Sadeghi M, Tavakol Afshari J, Esmaeili S, Mohammadi M Heliyon. 2023; 9(11):e21615.

PMID: 38027572 PMC: 10665754. DOI: 10.1016/j.heliyon.2023.e21615.

Immune Checkpoint Blockade Therapy for Breast Cancer: Lessons from Epithelial-Mesenchymal Transition.

OConnell I, Dongre A Mol Diagn Ther. 2023; 27(4):433-444.

PMID: 37193859 PMC: 10299941. DOI: 10.1007/s40291-023-00652-3.

MicroRNA: role in macrophage polarization and the pathogenesis of the liver fibrosis.

Yu W, Wang S, Wang Y, Chen H, Nie H, Liu L Front Immunol. 2023; 14:1147710.

PMID: 37138859 PMC: 10149999. DOI: 10.3389/fimmu.2023.1147710.

Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy.

Gu Y, Zhang Z, Ten Dijke P Cell Mol Immunol. 2023; 20(4):318-340.

PMID: 36823234 PMC: 10066239. DOI: 10.1038/s41423-023-00980-8.

References

Schmid P, Adams S, Rugo H, Schneeweiss A, Barrios C, Iwata H . Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22):2108-2121. DOI: 10.1056/NEJMoa1809615. View

Nagy A, Lanczky A, Menyhart O, Gyorffy B . Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018; 8(1):9227. PMC: 6003936. DOI: 10.1038/s41598-018-27521-y. View

Saji H, Koike M, Yamori T, Saji S, Seiki M, Matsushima K . Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer. 2001; 92(5):1085-91. DOI: 10.1002/1097-0142(20010901)92:5<1085::aid-cncr1424>3.0.co;2-k. View

Wang X, Seed B . A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res. 2003; 31(24):e154. PMC: 291882. DOI: 10.1093/nar/gng154. View

Deng J, Thennavan A, Shah S, Bagdatlioglu E, Klar N, Heguy A . Serial single-cell profiling analysis of metastatic TNBC during Nab-paclitaxel and pembrolizumab treatment. Breast Cancer Res Treat. 2020; 185(1):85-94. PMC: 8170702. DOI: 10.1007/s10549-020-05936-4. View

Zhao X, Qu J, Sun Y, Wang J, Liu X, Wang F . Prognostic significance of tumor-associated macrophages in breast cancer: a meta-analysis of the literature. Oncotarget. 2017; 8(18):30576-30586. PMC: 5444766. DOI: 10.18632/oncotarget.15736. View

Lin E, Nguyen A, Russell R, Pollard J . Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001; 193(6):727-40. PMC: 2193412. DOI: 10.1084/jem.193.6.727. View

Baird N, Bowlin J, Cohrs R, Gilden D, Jones K . Comparison of varicella-zoster virus RNA sequences in human neurons and fibroblasts. J Virol. 2014; 88(10):5877-80. PMC: 4019124. DOI: 10.1128/JVI.00476-14. View

Hulsen T, de Vlieg J, Alkema W . BioVenn - a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. BMC Genomics. 2008; 9:488. PMC: 2584113. DOI: 10.1186/1471-2164-9-488. View

10.

Armstrong C, Botella R, Galloway T, Murray N, Kramp J, Song I . Antitumor effects of granulocyte-macrophage colony-stimulating factor production by melanoma cells. Cancer Res. 1996; 56(9):2191-8. View

11.

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

12.

Edgar R, Domrachev M, Lash A . Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2001; 30(1):207-10. PMC: 99122. DOI: 10.1093/nar/30.1.207. View

13.

Tsai J, Yang J . Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 2013; 27(20):2192-206. PMC: 3814640. DOI: 10.1101/gad.225334.113. View

14.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

15.

Chick R, Clifton G, Hale D, Vreeland T, Hickerson A, Kemp Bohan P . Subgroup analysis of nelipepimut-S plus GM-CSF combined with trastuzumab versus trastuzumab alone to prevent recurrences in patients with high-risk, HER2 low-expressing breast cancer. Clin Immunol. 2021; 225:108679. DOI: 10.1016/j.clim.2021.108679. View

16.

Lehmann W, Mossmann D, Kleemann J, Mock K, Meisinger C, Brummer T . ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types. Nat Commun. 2016; 7:10498. PMC: 4756710. DOI: 10.1038/ncomms10498. View

17.

Christenson J, Butterfield K, Spoelstra N, Norris J, Josan J, Pollock J . MMTV-PyMT and Derived Met-1 Mouse Mammary Tumor Cells as Models for Studying the Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression. Horm Cancer. 2017; 8(2):69-77. PMC: 5407486. DOI: 10.1007/s12672-017-0285-6. View

18.

Vannini F, Kashfi K, Nath N . The dual role of iNOS in cancer. Redox Biol. 2015; 6:334-343. PMC: 4565017. DOI: 10.1016/j.redox.2015.08.009. View

19.

Pereira B, Chin S, Rueda O, Vollan H, Provenzano E, Bardwell H . The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016; 7:11479. PMC: 4866047. DOI: 10.1038/ncomms11479. View

20.

Chen L, Gibbons D, Goswami S, Cortez M, Ahn Y, Byers L . Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014; 5:5241. PMC: 4212319. DOI: 10.1038/ncomms6241. View