Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model
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Yinglong Zhang1,*, Qiong Ma1,*, Tao Liu1,*, Guofeng Guan2,*, Kailiang Zhang3, Jiayan Chen4, Nan Jia1, Shiju Yan1, Guanyin Chen1, Shiluan Liu1, Kuo Jiang1, Yao Lu1, Yanhua Wen1, Haien Zhao1, Yong Zhou1, Qingyu Fan1, Xiuchun Qiu1
1Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
2Department of Microsurgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China
3Department of Orthopedics, No. 88 Hospital of PLA, Tai’an, Shandong, China
4Department 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
Xiuchun Qiu, e-mail: [email protected]
Qingyu Fan, e-mail: [email protected]
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
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.
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