| Title: |
MicroRNA-200c restoration reveals a cytokine profile to enhance M1 macrophage polarization in breast cancer |
| 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 |
| Source: |
npj Breast Cancer, Vol 7, Iss 1, Pp 1-13 (2021) |
| Publisher Information: |
Nature Portfolio, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2374-4677 |
| Relation: |
https://doaj.org/toc/2374-4677 |
| DOI: |
10.1038/s41523-021-00273-1 |
| Access URL: |
https://doaj.org/article/60e89acc1885465fafd6cd0d4bea2bf5 |
| Accession Number: |
edsdoj.60e89acc1885465fafd6cd0d4bea2bf5 |
| Database: |
Directory of Open Access Journals |
