Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer

BMC Cancer

Research Article

Bipin Nair¹  Pramod K. Tiwari²  Rafael Guerrero-Preston³  David Sidransky³  Patricia Garcia⁴  Juan Carlos Roa⁴  Pamela Leal-Rojas⁵  Vani Santosh⁶  Nandini A. Sahasrabuddhe⁷  Remya Raja⁷  Tejaswini Subbannayya⁸  Santosh Renuse⁸  Vishalakshi Nanjappa⁸  T. S. Keshava Prasad⁹  Nazia Syed^1,10  Gajanan Sathe^1,11  Aditi Chatterjee^1,12  Arun H. Patil^1,13  Harsha Gowda^1,14  Sneha M. Pinto^1,14  Sanjay Navani^1,15  Mustafa A. Barbhuiya^1,16  Akhilesh Pandey^1,17 

[1] Amrita School of Biotechnology, Amrita University, 690525, Kollam, India;Centre for Genomics, Molecular and Human Genetics, Jiwaji University, 474011, Gwalior, India;School of Studies in Zoology, Jiwaji University, Gwalior, India;Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 21231, Baltimore, MD, USA;Department of Pathology, Advanced Center for Chronic Diseases (ACCDiS), CITO, Pontificia Universidad Católica de Chile, Santiago, Chile;Department of Pathology, Center of Genetic and Immunological Studies (CEGIN) and Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile;McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;Department of Pathology, National Institute of Mental Health and Neurosciences, 560029, Bangalore, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;Amrita School of Biotechnology, Amrita University, 690525, Kollam, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;Amrita School of Biotechnology, Amrita University, 690525, Kollam, India;YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, 575018, Mangalore, India;NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, 560029, Bangalore, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, 605014, Puducherry, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;Manipal University, Madhav Nagar, 576104, Manipal, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;Manipal University, Madhav Nagar, 576104, Manipal, India;YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, 575018, Mangalore, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;School of Biotechnology, KIIT University, 751024, Bhubaneswar, Odisha, India;Institute of Bioinformatics, International Technology Park, 560066, Bangalore, India;YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, 575018, Mangalore, India;Lab Surgpath, 400034, Mumbai, India;McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;Adrienne Helis Malvin Research Foundation, 70130, New Orleans, LA, USA;McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;Departments of Biological Chemistry, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;Departments of Oncology, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;Departments of Pathology, Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;

关键词: Gastrointestinal cancer;    RNA interference;    Functional inhibition;    Suicide substrate;    MIF;   

DOI  :  10.1186/s12885-015-1855-z

 received in 2015-02-18, accepted in 2015-10-27,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPoor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer.MethodsProteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach. The expression of macrophage migration inhibitory factor was analysed in gallbladder adenocarcinoma tissues using immunohistochemistry. In vitro cellular assays were carried out in a panel of gallbladder cancer cell lines using MIF inhibitors, ISO-1 and 4-IPP or its specific siRNA.ResultsThe quantitative proteomic experiment led to the identification of 3,653 proteins, among which 654 were found to be overexpressed and 387 were downregulated in the invasive cell lines (OCUG-1, NOZ and GB-d1) compared to the non-invasive cell line, TGBC24TKB. Among these, macrophage migration inhibitory factor (MIF) was observed to be highly overexpressed in two of the invasive cell lines. MIF is a pleiotropic proinflammatory cytokine that plays a causative role in multiple diseases, including cancer. MIF has been reported to play a central role in tumor cell proliferation and invasion in several cancers. Immunohistochemical labeling of tumor tissue microarrays for MIF expression revealed that it was overexpressed in 21 of 29 gallbladder adenocarcinoma cases. Silencing/inhibition of MIF using siRNA and/or MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the gallbladder cancer cells.ConclusionsOur findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer.

【 授权许可】

CC BY   
© Subbannayya et al. 2015