Abstract 4281: Oncostatin M renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-fluorouracil by inducing hepatocytic differentiation
Recent evidence suggests that a certain type of () is hierarchically organized by a subset of cells with stem cell features (stem cells; ). Although normal stem cells and are considered to share similar self-renewal programs， it remains unclear whether differentiation programs are also maintained in and effectively used for eradication. In this study， we investigated the effect of oncostatin M ()， an -related cytokine known to induce the differentiation of hepatoblasts into hepatocytes， on liver . receptor expression was detected in the majority of epithelial molecule-positive (EpCAM(+)) with stem/progenitor cell features. treatment resulted in the induction of hepatocytic differentiation of EpCAM(+) cells by inducing signal transducer and activator of 3 activation， as determined by a decrease in stemness-related gene expression， a decrease in EpCAM， alpha-fetoprotein and protein expressions， and an increase in albumin protein expression. -treated EpCAM(+) cells showed enhanced with expansion of the EpCAM-negative non-population. Noticeably， combination of treatment with the chemotherapeutic agent (5-FU)， which eradicates EpCAM-negative non-， dramatically increased the number of apoptotic cells in vitro and suppressed in vivo compared with either saline control， ， or 5-FU treatment alone. Taken together， our data suggest that could be effectively used for the differentiation and active of dormant EpCAM(+) liver ， and the combination of and conventional chemotherapy with 5-FU efficiently eliminates by targeting both and non-.