title: Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model.
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.
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Microsurgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Guan
authors.affiliation: Department of Orthopedics, No. 88 Hospital of PLA, Tai'an, Shandong, China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Shiju
authors.initials: S
authors.lastname: Yan
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Guanyin
authors.initials: G
authors.lastname: Chen
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Shiluan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Haien
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Orthopaedic Oncology Institute, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009366:Neoplasm Seeding; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D012516:Osteosarcoma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D053612:Janus Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: interleukin-6; metastasis; osteosarcoma; recurrence; tumour self-seeding by circulating tumour cells