MicroRNA-200c restoration reveals a cytokine profile to enhance M1 macrophage polarization in breast cancer
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 Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 27, 2021
- Source ID
- 10.1038/s41523-021-00273-1
Entities
People
- Claire L. Ihle
- Jennifer K Richer
- Jessica L Christenson
- Jill E Slansky
- Kathleen I. O’neill
- Michelle M. Williams
- Nicole S. Spoelstra
- Sabrina A. Hafeez
Organizations
- National Cancer Institute
- National Institutes of Health
- United States Department of Defense