Abstract

Identifying Potential Therapeutic Targets in Gallbladder Cancer using Proteomic Strategies

Tejaswini Subbannayya, Research Scientist, Institute of Bioinformatics

Gallbladder cancer (GBC) is the predominant form of biliary tract cancer. It often manifests at an advanced and unresectable stage. The malignancy is aggressive and the prognosis is dismal with a survival of less than 5 years in 90% of the cases. Early detection is incidental with surgery being the only curative option. Currently, neither are there reliable biomarkers for early diagnosis nor targeted therapy for the disease. This highlights the need to identify potential therapeutic targets to improve treatment options and disease outcome. To this end, proteomic strategies were employed to study the pathobiology in GBC using GBC cell lines. The GBC cell proteome was studied in four GBC cell lines based on their invasive property (non-invasive to highly invasive) using the isobaric tags for relative and absolute quantitation (iTRAQ) labeling-based quantitative proteomic approach. Among the dysregulated proteins, macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine reported to play a role in tumor cell proliferation and invasion in several cancer, was found to be overexpressed. Immunohistochemistry using tissue microarrays revealed overexpression of MIF in 72% of gallbladder adenocarcinoma cases tested. Silencing using MIF siRNA as well as functional inhibition using MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the GBC cells. Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for GBC.