Pharmacologic IL-6Rα inhibition in cholangiocarcinoma promotes cancer cell growth and survival

Publication date: Available online 9 November 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Florian Kleinegger, Eva Hofer, Christina Wodlej, Nicole Golob-Schwarzl, Anna Maria Birkl-Toeglhofer, Alexander Stallinger, Johannes Petzold, Anna Orlova, Stefanie Krassnig, Robert Reihs, Tobias Niedrist, Harald Mangge, Young Nyun Park, Michael Thalhammer, Ariane Aigelsreiter, Sigurd Lax, Christoph Garbers, Peter Fickert, Stefan Rose-John, Richard MorigglAbstractBiliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of the gallbladder (GBC) with a 5-year survival rate between 5 and 18% due to late diagnosis and rapid disease progression. Chronic inflammation is one of the main risk factors for CCA and GBC in particular. IL-6, as a mediator of inflammation, can act through a membrane-bound receptor alpha-chain (mIL-6R, “IL-6 classic signaling”) or via soluble forms (sIL-6R, “IL-6 trans-signaling”). However, little is known about the impact on cellular responses of IL-6 trans-signaling on BTC. We analyzed primary tumors as whole sections and as tissue microarrays, and also searched The Cancer Genome Atlas database. Compared to non-neoplastic, non-inflamed gallbladder tissue, IL-6Rα was downregulated in GBC, and this correlated with the patients' overall survival. Furthermore, different CCA cell lines and compounds for activation (IL-6 and Hyper-IL-6) or inhibition (...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research