Oncostatin M is overexpressed in NASH‐related hepatocellular carcinoma and promotes cancer cell invasiveness and angiogenesis

• DOI: 10.1002/path.5871
• Publication Date: 2022-01-22T09:33:48Z
• Authors: Giovanni Di Maira; Beatrice Foglia; Lucia Napione; Cristian Turato; Marina Maggiora; Salvatore Sutti; Erica Novo; Maria Alvaro; Riccardo Autelli; Sebastiano Colomb...; Federico Bussolino; Patrizia Carucci; Silvia Gaia; Chiara Rosso; Alessandra Biasiolo; Patrizia Pontisso; Elisabetta Bugianesi; Emanuele Albano; Fabio Marra; Maurizio Parola; Stefania Cannito
• Keywords: Oncostatin M; Steatohepatitis; Liver Cancer; Tumor progression

Oncostatin M (OSM) is a pleiotropic cytokine of the interleukin (IL)-6 family that contributes to progression chronic liver disease. Here we investigated role OSM in development and hepatocellular carcinoma (HCC) non-alcoholic fatty disease (NAFLD)/non-alcoholic steatohepatitis (NASH). The was (1) selected cohorts NAFLD/NASH HCC patients, (2) cancer cells exposed human recombinant or stably transfected overexpress OSM, (3) murine xenografts, (4) NASH-related model hepatic carcinogenesis. found be selectively overexpressed depending on tumor grade. serum levels, barely detectable patients with simple steatosis NASH, were increased cirrhosis more evident those carrying HCC. In this latter group, levels significantly higher subjects intermediate/advanced HCCs correlated poor survival. Cell culture experiments indicated upregulation by inducing epithelial-to-mesenchymal transition invasiveness as well angiogenesis, which critical relevance. overexpression associated slower growth but an rate lung metastases. Overexpression its positive correlation angiogenic switch also confirmed NAFLD/NASH-related hepatocarcinogenesis. Consistent this, analysis specimens from vascular invasion showed expressed invading vessels. conclusion, appears specific feature arising background, it correlates clinical parameters outcome. Our data highlight novel pro-carcinogenic contribution for NAFLD/NASH, suggesting factor prognostic marker putative potential target therapy. © 2022 Authors. Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.