Oncostatin M is overexpressed in NASH-related hepatocellular carcinoma and promotes a pro-tumorigenic inflammatory response. (March 2023)

• Record Type: Journal Article
• Authors: Foglia, B.; Cannito, S.; Sutti, S.; Nurcis, J.; Turato, C.; Maggiora, M.; Doto, F.; Rosso, C.; Carucci, P.; Gaia, S.; Biasiolo, A.; Pontisso, P.; Bugianesi, E.; Albano, E.; Parola, M.
• Is Part Of: Digestive and liver disease. Volume 55(2023)Supplement 1
• Page Start: S34
• Publication Date: 2023-03
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2023.01.066
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract : Introduction: Oncostatin M (OSM) is a pleiotropic cytokine belonging to the interleukin (IL)-6 family that has been proposed to contribute to the progression of chronic liver diseases, hepatocellular carcinoma (HCC) development and metastasis. High levels of OSM was observed in cirrhotic patients with different etiology carrying HCC. Aim: Here we investigated the role of OSM in relation to the development of HCC in non-alcoholic steatohepatitis (NASH) background. Methods: We investigated the role of OSM in NASH-related HCC taking advantage of: a) cohort of NASH patients with/without HCC; b) mouse model of NASH-related liver carcinogenesis (DEN/CDAA protocol); c) human macrophage cell lines exposed to human recombinant OSM (hrOSM) . Results: OSM serum levels are significantly higher in patients carrying NASH-related HCC, as compared to those whit viral aetiologies, and their increase is paralleled the disease progression from simple steatosis to HCC. Noteworthy, OSM serum levels are significantly higher in patients with intermediate/advanced HCC and correlate with poor survival. In patients with NASH-related HCC, OSM is expressed in cancer cells in relation to the staging of HCC as well as to macrophages infiltrating tumour. Accordingly, OSM expression is increased in murine NASH-related liver tumours and correlates with F4/80 gene expression, suggesting an interplay between OSM and macrophages recruitment/functions in the tumor microenvironment. In particular, OSM transcript levels correlate with canonical M1and M2 macrophage polarization markers and with newly identified NASH-associated macrophages (NAM) markers (TREM-2, CD-9). The ability of OSM to promote M2 polarization, observed in human THP1 macrophages exposed to hrOSM, is due to activation of STAT3 and PI-3K/Akt signaling pathways. Conclusions: Patients with HCC arising on a NASH background showed increased OSM serum levels that correlate with clinical parameters and disease outcome. Experimental data highlight a pro-carcinogenic contribution for OSM in NASH, by promoting pro-tumorigenic inflammation and eventually modulating tumor escape.