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

// Yin Ji Piao 1, 2, * , Hoe Suk Kim 1, * , Eun Hye Hwang 1 , Jisu Woo 1 , Meihua Zhang 1, 3 and Woo Kyung Moon 1, 2 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 * These authors contributed equally to this work Correspondence to: Woo Kyung Moon, email: moonwk@snu.ac.kr 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.