Limits...
Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma.

Tamai K, Nakamura M, Mizuma M, Mochizuki M, Yokoyama M, Endo H, Yamaguchi K, Nakagawa T, Shiina M, Unno M, Muramoto K, Sato I, Satoh K, Sugamura K, Tanaka N - Cancer Sci. (2014)

Bottom Line: Its malignant phenotypes may be assumed by cancer stem cells (CSC).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.

View Article: PubMed Central - PubMed

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

Related in: MedlinePlus

Interconversion of the CD274high and CD274low states in vitro. RBE (a) or HuCCT1 (b) cells were sorted using FACSAria and cultured under normal conditions. After incubation for the indicated times, the cells were stained with an anti-CD274 antibody and analyzed using flow cytometry. (c) Immunohistochemistry of tumor cells 38 weeks after the engraftment of CD274low cells into immunodeficient NOD/scid/γc mice. Bar, 100 μm. The tumor was fixed and stained with anti-CD274 (brown) and anti-Ki-67 (red) antibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4317902&req=5

fig03: Interconversion of the CD274high and CD274low states in vitro. RBE (a) or HuCCT1 (b) cells were sorted using FACSAria and cultured under normal conditions. After incubation for the indicated times, the cells were stained with an anti-CD274 antibody and analyzed using flow cytometry. (c) Immunohistochemistry of tumor cells 38 weeks after the engraftment of CD274low cells into immunodeficient NOD/scid/γc mice. Bar, 100 μm. The tumor was fixed and stained with anti-CD274 (brown) and anti-Ki-67 (red) antibodies.

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.


Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma.

Tamai K, Nakamura M, Mizuma M, Mochizuki M, Yokoyama M, Endo H, Yamaguchi K, Nakagawa T, Shiina M, Unno M, Muramoto K, Sato I, Satoh K, Sugamura K, Tanaka N - Cancer Sci. (2014)

Interconversion of the CD274high and CD274low states in vitro. RBE (a) or HuCCT1 (b) cells were sorted using FACSAria and cultured under normal conditions. After incubation for the indicated times, the cells were stained with an anti-CD274 antibody and analyzed using flow cytometry. (c) Immunohistochemistry of tumor cells 38 weeks after the engraftment of CD274low cells into immunodeficient NOD/scid/γc mice. Bar, 100 μm. The tumor was fixed and stained with anti-CD274 (brown) and anti-Ki-67 (red) antibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317902&req=5

fig03: Interconversion of the CD274high and CD274low states in vitro. RBE (a) or HuCCT1 (b) cells were sorted using FACSAria and cultured under normal conditions. After incubation for the indicated times, the cells were stained with an anti-CD274 antibody and analyzed using flow cytometry. (c) Immunohistochemistry of tumor cells 38 weeks after the engraftment of CD274low cells into immunodeficient NOD/scid/γc mice. Bar, 100 μm. The tumor was fixed and stained with anti-CD274 (brown) and anti-Ki-67 (red) antibodies.
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.

Bottom Line: Its malignant phenotypes may be assumed by cancer stem cells (CSC).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.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus