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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer

Authors: Tejaswini Subbannayya, Pamela Leal-Rojas, Mustafa A. Barbhuiya, Remya Raja, Santosh Renuse, Gajanan Sathe, Sneha M. Pinto, Nazia Syed, Vishalakshi Nanjappa, Arun H. Patil, Patricia Garcia, Nandini A. Sahasrabuddhe, Bipin Nair, Rafael Guerrero-Preston, Sanjay Navani, Pramod K. Tiwari, Vani Santosh, David Sidransky, T. S. Keshava Prasad, Harsha Gowda, Juan Carlos Roa, Akhilesh Pandey, Aditi Chatterjee

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Poor 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.

Methods

Proteomic 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.

Results

The 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.

Conclusions

Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer.
Appendix
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Metadata
Title
Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer
Authors
Tejaswini Subbannayya
Pamela Leal-Rojas
Mustafa A. Barbhuiya
Remya Raja
Santosh Renuse
Gajanan Sathe
Sneha M. Pinto
Nazia Syed
Vishalakshi Nanjappa
Arun H. Patil
Patricia Garcia
Nandini A. Sahasrabuddhe
Bipin Nair
Rafael Guerrero-Preston
Sanjay Navani
Pramod K. Tiwari
Vani Santosh
David Sidransky
T. S. Keshava Prasad
Harsha Gowda
Juan Carlos Roa
Akhilesh Pandey
Aditi Chatterjee
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1855-z

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