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Oncotarget. 2017 Dec 13;9(7):7398-7410. doi: 10.18632/oncotarget.23238. eCollection 2018 Jan 26.

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

Author information

1
Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Jongno-Gu, Seoul 03080, Korea.
2
Department of Biomedical Sciences, Seoul National University College of Medicine, Jongno-Gu, Seoul 03080, Korea.
3
Department of Radiology, Yanbian University Hospital, Yanji City, Jilin Province 133000, China.

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.

KEYWORDS:

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

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