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Macrophage migration inhibitory factor promotes osteosarcoma growth and lung metastasis through activating the RAS/MAPK pathway

Wang, Chen ; Zhou, Xing ; Li, Wentao ; Li, Mingyue ; Tu, Tingyue ; Ba, Ximing ; Wu, Yinyu ; Huang, Zhen ; Fan, Gentao ; Zhou, Guangxin ; Wu, Sujia ; Zhao, Jianning ; Zhang, Junfeng ; Chen, Jiangning

Cancer letters, 2017-09, Vol.403, p.271-279 [Peer Reviewed Journal]

Ireland: Elsevier B.V

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Title:
Macrophage migration inhibitory factor promotes osteosarcoma growth and lung metastasis through activating the RAS/MAPK pathway
Author: Wang, Chen ; Zhou, Xing ; Li, Wentao ; Li, Mingyue ; Tu, Tingyue ; Ba, Ximing ; Wu, Yinyu ; Huang, Zhen ; Fan, Gentao ; Zhou, Guangxin ; Wu, Sujia ; Zhao, Jianning ; Zhang, Junfeng ; Chen, Jiangning
Subjects: Adolescent ; Animals ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Bone cancer ; Bone Neoplasms - drug therapy ; Bone Neoplasms - enzymology ; Bone Neoplasms - genetics ; Bone Neoplasms - pathology ; Breast cancer ; Cancer therapies ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cisplatin ; Cisplatin - pharmacology ; Cytokines ; Dose-Response Relationship, Drug ; Doxorubicin ; Doxorubicin - pharmacology ; Extracellular signal-regulated kinase ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Hematology, Oncology and Palliative Medicine ; Humans ; Immunotherapy ; Intramolecular Oxidoreductases - genetics ; Intramolecular Oxidoreductases - metabolism ; Intramolecular Oxidoreductases - pharmacology ; Kinases ; Laboratory animals ; Leukocyte migration ; Liver cancer ; Lung cancer ; Lung metastasis ; Lung Neoplasms - enzymology ; Lung Neoplasms - genetics ; Lung Neoplasms - prevention & control ; Lung Neoplasms - secondary ; Lungs ; Macrophage migration inhibitory factor ; Macrophage Migration-Inhibitory Factors - genetics ; Macrophage Migration-Inhibitory Factors - metabolism ; Macrophage Migration-Inhibitory Factors - pharmacology ; Macrophages ; Male ; MAP kinase ; Medical prognosis ; Metastases ; Metastasis ; Mice, Inbred BALB C ; Mice, Nude ; Mitogen-Activated Protein Kinases - metabolism ; Osteosarcoma ; Osteosarcoma - drug therapy ; Osteosarcoma - enzymology ; Osteosarcoma - genetics ; Osteosarcoma - secondary ; Patients ; Proteins ; ras Proteins - metabolism ; RAS/MAPK pathway ; RNA Interference ; Sarcoma ; Sensitivity enhancement ; Signal transduction ; Signal Transduction - drug effects ; Survival Analysis ; Time Factors ; Transfection ; Tumor Burden ; Tumor Microenvironment ; Tumors ; Tumour growth ; Xenograft Model Antitumor Assays ; Xenografts
Is Part Of: Cancer letters, 2017-09, Vol.403, p.271-279
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Description: Abstract Emerging evidence suggests that the tumour microenvironment plays a critical role in osteosarcoma (OS) development. Thus, cytokine immunotherapy could be a novel strategy for OS treatment. In this study, we explored the role of macrophage migration inhibitory factor (MIF), an important cytokine in OS progression, and investigated the anti-tumour effects of targeting MIF in OS. The results showed that MIF significantly increased in the tissue and serum samples of OS patients and was associated with tumour size, pulmonary metastasis and the survival rate of OS patients. We verified a positive correlation between MIF and p-ERK1/2 in OS patients. The in vitro results indicated that MIF could activate the RAS/MAPK pathway in a time- and dose-dependent manner, thereby promoting cell proliferation and migration. Furthermore, shRNA targeting MIF significantly inhibited tumour growth and lung metastasis in a mouse xenograft model and orthotopic model of OS. Additionally, inhibition of MIF significantly enhanced the sensitivity of OS cells to cisplatin and doxorubicin. Our findings suggest that immunotherapy targeting MIF to block the RAS/MAPK kinase cascade may represent a feasible and promising approach for OS treatment.
Publisher: Ireland: Elsevier B.V
Language: English

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Macrophage migration inhibitory factor promotes osteosarcoma growth and lung metastasis through activating the RAS/MAPK pathway

Wang, Chen ; Zhou, Xing ; Li, Wentao ; Li, Mingyue ; Tu, Tingyue ; Ba, Ximing ; Wu, Yinyu ; Huang, Zhen ; Fan, Gentao ; Zhou, Guangxin ; Wu, Sujia ; Zhao, Jianning ; Zhang, Junfeng ; Chen, Jiangning

Ireland: Elsevier B.V

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