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: We then investigated the plasticity of the CD274low populations of RBE and HuCCT1 cells. The CD274low and CD274high cells were cultured and stained for CD274 periodically during in vitro culture. The RBE CD274low cells showed an increase of CD274 expression and shifted to a CD274high state at day 3 of culture, and vice versa, the RBE CD274high cells showed a decrease of CD274 expression (Fig.3a). Similar shifts of CD274 expression were observed on the CD274low and CD274high populations of HuCCT1 cells, although the HuCCT1 CD274low cells started to shift to a CD274high state within 24 h of culture (Fig.3b). These results suggest that the CD274low cells have plasticity in vitro. Next, we investigated the characteristics associated with the in vivo plasticity of RBE CD274low cells. Tumors formed in NOG mice engrafted with the RBE CD274low cells were analyzed for the expression of CD274 and Ki-67 using immunohistochemistry. CD274 was expressed predominantly at the periphery of tumor nodules, as was Ki-67 (Fig.3c). These results suggest that the CD274low cells possess plasticity and are in a dormant state in vivo.
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.