Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model

// Yinglong Zhang 1, * , Qiong Ma 1, * , Tao Liu 1, * , Guofeng Guan 2, * , Kailiang Zhang 3 , Jiayan Chen 4 , Nan Jia 1 , Shiju Yan 1 , Guanyin Chen 1 , Shiluan Liu 1 , Kuo Jiang 1 , Yao Lu 1 , Yanhua Wen 1 , Haien Zhao 1 , Yong Zhou 1 , Qingyu Fan 1 , Xiuchun Qiu 1 1 Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China 2 Department of Microsurgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China 3 Department of Orthopedics, No. 88 Hospital of PLA, Tai’an, Shandong, China 4 Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi’an, Shaanxi, China * These authors have contributed equally to this work Correspondence to: Xiuchun Qiu, e-mail: xiuchun_qiu@yeah.net Qingyu Fan, e-mail: qingyu_fan@yeah.net Keywords: osteosarcoma, tumour self-seeding by circulating tumour cells, interleukin-6, metastasis, recurrence Received: June 15, 2015      Accepted: October 29, 2015      Published: November 09, 2015 ABSTRACT Tumour self-seeding by circulating tumour cells (CTCs) enhances tumour progression and recurrence. Previously, we demonstrated that tumour self-seeding by CTCs occurs in osteosarcoma and revealed that interleukin-6 (IL-6) may promote CTC attraction. Here, we investigated the underlying mechanisms of IL-6 in tumour self-seeding by CTCs. IL-6 suppression inhibited in vitro cell proliferation, migration, and invasion. In addition, rhIL-6 activated the Janus-activated kinase/signal transducers and activators of transcription 3 (JAK/STAT3) and mitogen-activated protein kinase/extracellular-signal regulated kinase1/2 (MAPK/ERK1/2) pathways in vitro . Both pathways increased cell proliferation, but only the JAK/STAT3 pathway promoted migration. Suppressing IL-6 inhibited in vivo tumour growth and metastasis. IL-6 suppression or JAK/STAT3 pathway inhibition reduced CTC seeding in primary tumours. Collectively, IL-6 promotes tumour self-seeding by CTCs in a nude mouse model. This finding may provide a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence.