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: To investigate whether CD274 is involved in tumor initiation, we sorted a human cholangiocarcinoma cell line, RBE cells based on their expression of CD274 (Fig. S1), and the CD274low and CD274high cells were then xenografted into immunodeficient NOD/scid/γc (NOG) mice. The CD274low population (1 x 104 cells) formed tumors at all six (6/6) injection sites, whereas the CD274high population formed tumors in one out of six (1/6) injection sites after 25 weeks of xenograft (Fig.1a, Table1A). We also examined the relationship between the expression level of CD274 and the tumorigenic potential using another human cholangiocarcinoma cell line, HuCCT1. The CD274low population (1 × 102 cells) of HuCCT1 formed tumors at three out of four (3/4) injection sites, whereas the CD274high population formed no (0/4) tumor after 23 weeks of xenograft (Fig.1b, Table1B). These results suggest that the CSC of cholangiocarcinoma are enriched in the CD274low population.
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.