TY - JOUR
T1 - Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer
AU - Subbannayya, Tejaswini
AU - Leal-Rojas, Pamela
AU - Barbhuiya, Mustafa A.
AU - Raja, Remya
AU - Renuse, Santosh
AU - Sathe, Gajanan
AU - Pinto, Sneha M.
AU - Syed, Nazia
AU - Nanjappa, Vishalakshi
AU - Patil, Arun H.
AU - Garcia, Patricia
AU - Sahasrabuddhe, Nandini A.
AU - Nair, Bipin
AU - Guerrero-Preston, Rafael
AU - Navani, Sanjay
AU - Tiwari, Pramod K.
AU - Santosh, Vani
AU - Sidransky, David
AU - Prasad, T. S.Keshava
AU - Gowda, Harsha
AU - Roa, Juan Carlos
AU - Pandey, Akhilesh
AU - Chatterjee, Aditi
N1 - Publisher Copyright:
© 2015 Subbannayya et al.
PY - 2015/11/4
Y1 - 2015/11/4
N2 - 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.
AB - 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.
KW - Functional inhibition
KW - Gastrointestinal cancer
KW - MIF
KW - RNA interference
KW - Suicide substrate
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U2 - 10.1186/s12885-015-1855-z
DO - 10.1186/s12885-015-1855-z
M3 - Article
C2 - 26530123
AN - SCOPUS:84946213538
SN - 1471-2407
VL - 15
JO - BMC cancer
JF - BMC cancer
IS - 1
M1 - 843
ER -