MicroRNA-200c restoration reveals a cytokine profile to enhance M1 macrophage polarization in breast cancer

Year: 2021

Type: article

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.

Source: npj Breast Cancer

DOI: 10.1038/s41523-021-00273-1

Authors: Michelle M. Williams, Jessica L. Christenson, Kathleen I. O’Neill, Sabrina A. Hafeez, Claire L. Ihle, Nicole S. Spoelstra, Jill E. Slansky, Jennifer K. Richer

Institution: University of Colorado Anschutz

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,170

Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, National Institutes of Health, Cancer Center, University of Colorado, National Cancer Institute

OpenAlex ID: W3164906484