Research Paper Volume 13, Issue 7 pp 10415—10430
Exosomal miR-222 from adriamycin-resistant MCF-7 breast cancer cells promote macrophages M2 polarization via PTEN/Akt to induce tumor progression
- 1 Department of Breast Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- 2 Post-Doctoral Working Station, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- 3 Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
- 4 Department of Pathology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- 5 Key Laboratory of Antibody Technology, The National Health and Family Planning Commission, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
- 6 Department of General Surgery, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
Received: November 11, 2020 Accepted: March 5, 2021 Published: March 22, 2021
https://doi.org/10.18632/aging.202802How to Cite
Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Exosome-mediated intercellular communication is considered to be an effective mode for malignant cells to transform biological behaviors in stromal cells. However, the mechanisms by which exosomes modulate macrophages within tumor microenvironment remain largely unclear. In this study, we found that both adriamycin-resistant breast cancer (BCa) cells and the corresponding exosomes (A/exo) were capable of inducing macrophages M2 polarization, which promoted the mobility, proliferation, migration and invasion of BCa cells. Since exosomes deliver microRNAs to affect cellular functions in recipient cells, we confirmed that miR-222 was significantly enriched in A/exo and could be successfully transferred to macrophages. Increased miR-222 level was also detected in exosomes derived from plasma and tissues of chemoresistant patients. Moreover, exosomal miR-222 from A/exo polarized M2 macrophages by targeting PTEN and activating Akt signaling pathway, which promoted BCa cells progression in a feed back loop. Co-culture of adriamycin-resistant BCa cells with macrophages in which miR-222 was upregulated or treated with A/exo facilitated tumor growth in vivo. Collectively, our data demonstrated that chemoresistant BCa cells could remodel macrophages within tumor microenvironment by secreting exosomal miR-222, which directly targeted PTEN and caused Akt cascade activation and macrophages M2 polarization. Our findings may provide a foundation for a promising strategy of BCa treatment by targeting exosomes or exosomal miR-222.