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

Oncostatin M Steatohepatitis Liver Cancer Tumor progression
DOI: 10.1002/path.5871 Publication Date: 2022-01-22T09:33:48Z
ABSTRACT
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.
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