Oncotarget

Research Papers:

Breast cancer cell-derived exosomes and macrophage polarization are associated with lymph node metastasis

Yin Ji Piao, Hoe Suk Kim, Eun Hye Hwang, Jisu Woo, Meihua Zhang and Woo Kyung Moon _

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Oncotarget. 2018; 9:7398-7410. https://doi.org/10.18632/oncotarget.23238

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Abstract

Yin Ji Piao1,2,*, Hoe Suk Kim1,*, Eun Hye Hwang1, Jisu Woo1, Meihua Zhang1,3 and Woo Kyung Moon1,2

1Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Jongno-Gu, Seoul 03080, Korea

2Department of Biomedical Sciences, Seoul National University College of Medicine, Jongno-Gu, Seoul 03080, Korea

3Department of Radiology, Yanbian University Hospital, Yanji City, Jilin Province 133000, China

*These authors contributed equally to this work

Correspondence to:

Woo Kyung Moon, email: [email protected]

Keywords: exosome; triple-negative breast cancer; lymph node; metastasis; macrophage

Received: September 15, 2017     Accepted: December 01, 2017     Published: December 13, 2017

ABSTRACT

Crosstalk between breast cancer and macrophages has potential implications for tumor metastasis. This study investigates macrophage polarization induced by triple-negative breast cancer (TNBC) cell-derived exosomes that promote lymph node (LN) metastasis in orthotopic TNBC models. The MDA-MB-231 cancer cell line expressing the exosomal CD63-red fluorescence (RFP) fusion protein was generated to noninvasively visualize exosome transfer into cancer cells and macrophages. Administration of RFP-tagged exosomes enhanced migration of macrophages and induced macrophage polarization in vitro. In orthotopic TNBC models, noninvasive bioluminescent imaging, ultrasound-guided photoacoustic imaging, and histological analysis revealed that intravenous injection of RFP-tagged exosomes promoted primary tumor growth and axillary LN metastasis in which expression of CD206, a marker or alternatively activated type 2 (M2) macrophages, was significantly higher than expression of NOS2, a marker of classically activated type 1 (M1) macrophages. These results suggest breast cancer cell-derived exosomes stimulate macrophage polarization that creates favorable conditions for LN metastatic processes in TNBC.


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