Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma.
Bottom Line: Furthermore, the CD274(low) cells possess several CSC-related characteristics, such as high aldehyde dehydrogenase (ALDH) activity, reduced reactive oxygen species production and a dormant state in the cell cycle.Furthermore, depletion of CD274 expression by shRNA in RBE cells enhances their tumorigenicity and increases ALDH activity.These results strongly suggest that CD274 has a novel function in the negative regulation of CSC-related phenotypes in human cholangiocarcinoma, which is distinct from its immunomodulatory actions.
Affiliation: Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Japan; Department of Cancer Science, Tohoku University Graduate School of Medicine, Sendai, Japan.Show MeSH
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Mentions: Last, we addressed the relationship between CD274 expression in clinical specimens and the prognosis of patients with cholangiocarcinoma. Tumor tissue specimens were completely resected from 91 patients with cholangiocarcinoma, as assessed both surgically and histologically. Anti-CD274 antibody staining showed high CD274 expression in the normal extrahepatic ductal areas (Fig.5a). In cancerous areas, CD274 was homogeneously expressed in the ductal regions, but ranged from weak to strong (Fig.5b,c) among the samples. We then divided the samples into two groups, CD274−/+ and CD274++, according to the expression level of CD274 in their cancerous areas, and compared the overall survival of patients using the Kaplan–Meier methods. The CD274−/+ group showed a significantly shorter median survival time than the CD274+/+ group (P = 0.0157; Fig.5d). There was no significant correlation between the expression level of CD274 and clinical demographics including age, sex or pathological stage of the cancer (Table S2). These results indicate that a lower expression of CD274 is correlated with a poorer prognosis in cholangiocarcinoma.
Affiliation: Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Japan; Department of Cancer Science, Tohoku University Graduate School of Medicine, Sendai, Japan.