J Cancer
2019; 10(13):2892-2906.
doi:10.7150/jca.31241 This issueCite
Research Paper
Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis
Xiuyan Yu1, Qun Zhang1, Xuehui Zhang1, Qing Han1, Hui Li1, Yiqing Mao1, Xi Wang1, Hongyan Guo2,✉, David M. Irwin3,✉, Gang Niu4,✉, Huanran Tan1,✉
1. Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China 2. Department of Gynaecology and Obstetrics, Peking University Third Hospital, Beijing 100191, China 3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada 4. Beijing N&N Genetech Company, Beijing 100082, China
✉ Corresponding authors: Prof. Huanran Tan, Department of Pharmacology Peking University, Health Science Center Physiology Building#232, 38 Xue Yuan Road Beijing 100191, China. Tel: +86 10 82802004; Fax: +86 10 82802004; E-mail: tanlabedu.cn. Prof. David M. Irwin, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Tel.: +1-416-978-0519; Fax: +1-416-978-5959 (D.M.I.); E-Mail: david.irwinca. Mr Gang Niu, Beijing N&N Genetech Company, Beijing, 100082, China. Tel.: +86-10-6404-7343 (G.N.); Fax: +86-10-6403-1254 (G.N.); E-Mail: nngenecom. Prof. Hongyan Guo, Department of Gynaecology and Obstetrics, Peking University Third Hospital, Beijing 100191, China. Tel./Fax: +86-10-82266699 (H.G.); E-Mail: bysyghycom.More
Citation:
Yu X, Zhang Q, Zhang X, Han Q, Li H, Mao Y, Wang X, Guo H, Irwin DM, Niu G, Tan H. Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis. J Cancer 2019; 10(13):2892-2906. doi:10.7150/jca.31241. https://www.jcancer.org/v10p2892.htm
Exosomes have recently become the subject of increasing research interest. Interactions between tumor and host cells via exosomes play crucial roles in the initiation, progression and invasiveness of breast cancer. In our study, we used exosomes isolated from a co-culture model of THP-1-derived macrophages exposed to apoptotic MCF-7 or MDA-MB-231 breast cancer cell line cells to investigate their effects on naïve MCF-7 or MDA-MB-231 cells in vitro and in vivo. This post-chemotherapy tumor microenvironment model allowed us to explore possible mechanisms that explain increased proliferation and metastasis of breast cancer seen in some patients. Our results suggest that while exosomes derived from macrophages normally inhibit proliferation and metastasis of MCF-7 or MDA-MB-231 cells, exposure of macrophages to breast cancer cells that have experienced chemotherapy are modified them to promote these processes. Exosomes from macrophages exposed to apoptotic cancer cells have increased amounts of IL-6 that increases the phosphorylation of STAT3, which likely explains the increased transcription of STAT3 target genes such as CyclinD1, MMP2 and MMP9. These observations suggest that the inhibition of exosome secretion and STAT3 signaling pathway activation might suppress the growth and metastasis of malignant tumors, and provide new targets for therapeutic treatment of malignant tumors after chemotherapy.
Keywords: exosome, apoptosis, metastasis, STAT3, breast cancer
Citation styles
APA
Yu, X., Zhang, Q., Zhang, X., Han, Q., Li, H., Mao, Y., Wang, X., Guo, H., Irwin, D.M., Niu, G., Tan, H. (2019). Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis. Journal of Cancer, 10(13), 2892-2906. https://doi.org/10.7150/jca.31241.
ACS
Yu, X.; Zhang, Q.; Zhang, X.; Han, Q.; Li, H.; Mao, Y.; Wang, X.; Guo, H.; Irwin, D.M.; Niu, G.; Tan, H. Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis. J. Cancer 2019, 10 (13), 2892-2906. DOI: 10.7150/jca.31241.
NLM
Yu X, Zhang Q, Zhang X, Han Q, Li H, Mao Y, Wang X, Guo H, Irwin DM, Niu G, Tan H. Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis. J Cancer 2019; 10(13):2892-2906. doi:10.7150/jca.31241. https://www.jcancer.org/v10p2892.htm
CSE
Yu X, Zhang Q, Zhang X, Han Q, Li H, Mao Y, Wang X, Guo H, Irwin DM, Niu G, Tan H. 2019. Exosomes from Macrophages Exposed to Apoptotic Breast Cancer Cells Promote Breast Cancer Proliferation and Metastasis. J Cancer. 10(13):2892-2906.
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