Panoply™ Human OSM Over-expressing Stable Cell Line

Oncostatin M (OSM) is a pleiotropic cytokine belonging to the interleukin (IL)-6 family that is implicated in the progression of chronic liver disease. Here, researchers investigated the role of OSM in the development and progression of hepatocellular carcinoma (HCC) within the context of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The study found that OSM is selectively upregulated in HCC cells from patients with NAFLD/NASH, with expression levels correlating with tumor grade. Serum OSM levels were very low in patients with simple steatosis or NASH but elevated in patients with cirrhosis, and even more markedly increased in those with concurrent HCC. Cell culture experiments demonstrated that OSM upregulation in liver cancer cells promotes HCC progression by inducing epithelial-mesenchymal transition (EMT), enhancing cancer cell invasiveness, and-crucially-inducing angiogenesis. In mouse xenograft models, OSM overexpression was associated with slower tumor growth but an increased rate of pulmonary metastasis. OSM overexpression and its positive correlation with the "angiogenic switch" were also confirmed in a mouse model of NAFLD/NASH-associated hepatocarcinogenesis. Consistent with these findings, analysis of human NASH-associated HCC liver specimens with vascular invasion revealed that the cancer cells invading the hepatic vasculature expressed OSM. In summary, OSM upregulation appears to be a specific feature of HCC arising in the context of NAFLD/NASH and is associated with clinical parameters and disease prognosis.

Given that epithelial-mesenchymal transition (EMT) is a pivotal event in tumor development and progression, researchers analyzed EMT markers in HepG2 cells treated with human recombinant OSM (hrOSM) or in HepG2 cells stably transfected to overexpress OSM (H/OSM). In both models, OSM induced characteristic morphological changes associated with EMT, including the loss of cell-cell contacts, dissociation from cell clusters, and the acquisition of a spindle-shaped or fibroblast-like phenotype (Figure 1A). Consistent with these changes, OSM downregulated E-cadherin expression at the cell membrane (Figure 1B), significantly enhanced the cells' ability to penetrate the Matrigel matrix (Figure 1C), and upregulated MMP2 levels (Figure 1D). Furthermore, hrOSM treatment or OSM overexpression triggered the rapid phosphorylation and activation of STAT3 (Figure 1E). OSM was also associated with the upregulation of transglutaminase 2 (TGM2) (Figure 1F); upon translocation to the cell membrane, TGM2 physically interacts with integrin α5β1 and acts as a co-receptor for fibronectin, thereby promoting cell migration and invasion. Accordingly, the OSM-induced upregulation of TGM2 was accompanied by elevated levels of fibronectin (Figure 1G).

Figure 1. OSM induces typical EMT changes and increased invasiveness. (Di Maira G, et al., 2022)