Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model
| Autor: | Xiuchun Qiu, Yao Lu, Haien Zhao, Yinglong Zhang, Tao Liu, Yanhua Wen, Nan Jia, Shiju Yan, Jiayan Chen, Qing-yu Fan, Shiluan Liu, Guanyin Chen, Yong Zhou, Qiong Ma, Kailiang Zhang, Kuo Jiang, Guofeng Guan |
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| Rok vydání: | 2015 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine MAPK/ERK pathway Pathology medicine.medical_specialty recurrence Blotting Western Transplantation Heterologous Mice Nude Bone Neoplasms Cell Line Metastasis 03 medical and health sciences Neoplasm Seeding 0302 clinical medicine Nude mouse osteosarcoma Cell Line Tumor medicine metastasis Animals Humans STAT3 Janus Kinases biology Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Cell growth Kinase business.industry Neoplastic Cells Circulating biology.organism_classification medicine.disease 030104 developmental biology Microscopy Fluorescence Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Osteosarcoma Female RNA Interference tumour self-seeding by circulating tumour cells Mitogen-Activated Protein Kinases Janus kinase business Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // 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. |
| Databáze: | OpenAIRE |
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