Research Papers:

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

Yinglong Zhang, Qiong Ma, Tao Liu, Guofeng Guan, Kailiang Zhang, Jiayan Chen, Nan Jia, Shiju Yan, Guanyin Chen, Shiluan Liu, Kuo Jiang, Yao Lu, Yanhua Wen, Haien Zhao, Yong Zhou, Qingyu Fan and Xiuchun Qiu _

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Oncotarget. 2016; 7:446-458. https://doi.org/10.18632/oncotarget.6371

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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

Correspondence to:

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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