Due to its tendency to recur and acquire chemoresistance quickly, bladder cancer (BC) remains to be an elusive and difficult disease. Patients with recurrent and chemoresistant BC have an extremely poor prognosis. One possible approach that may provide insightful and valuable information regarding resistance mechanisms is looking into the lipid metabolism of BC cells. Metabolism of lipids is essential for cancer cells and is associated with the regulation of a variety of key cellular processes and functions. This study conducted a comparative lipidomic profiling of two isogenic human T24 bladder cancer cell lines, one of which is clinically characterized as cisplatin-sensitive (T24S) and the other as cisplatin-resistant (T24R). Immunohistochemistry analysis revealed that expression of cytosolic acetyl-CoA synthetase 2 (ACSS2) is positively correlated with aggressive BC. Ultra performance liquid chromatography-mass spectrometry (UPLC-MS) analysis profiled a total of 1,864 lipids and levels of differentially expressed lipids suspected of being associated with cisplatin resistance were determined. In addition, we found that ACSS2 inhibition greatly perturbed levels of metabolites, including CE(18:1), CE(22:6), TG(49:1), and TG(53:2). This study broadens our current knowledge on the links between cisplatin resistance and lipid metabolism in aggressive BC and suggests potential biomarkers for identifying higher-risk patients.
Oncotarget. 2018 Jan 13*** epublish ***
Min Young Lee, Austin Yeon, Muhammad Shahid, Eunho Cho, Vikram Sairam, Robert Figlin, Khae-Hwan Kim, Jayoung Kim
Institute for Systems Biology, Seattle, WA, USA., Department of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., University of California Los Angeles, Los Angeles, CA, USA., Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Department of Urology, Ga Cheon University College of Medicine, Incheon, South Korea.