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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.

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CD274 expression in cholangiocarcinoma specimens and prognosis of cholangiocarcinoma patients. (a) Normal bile duct staining with an anti-CD274 antibody. Bar, 100 μm. (b,c) Representative results of the anti-CD274 staining of clinical specimens obtained from 91 patients by surgical resection. CD274 immunohistochemistry was scored as described in Materials and Methods. Bar, 100 μm. (d) Kaplan–Meier analysis for the disease-specific survival rate of the two groups.
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fig05: CD274 expression in cholangiocarcinoma specimens and prognosis of cholangiocarcinoma patients. (a) Normal bile duct staining with an anti-CD274 antibody. Bar, 100 μm. (b,c) Representative results of the anti-CD274 staining of clinical specimens obtained from 91 patients by surgical resection. CD274 immunohistochemistry was scored as described in Materials and Methods. Bar, 100 μm. (d) Kaplan–Meier analysis for the disease-specific survival rate of the two groups.

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.


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)

CD274 expression in cholangiocarcinoma specimens and prognosis of cholangiocarcinoma patients. (a) Normal bile duct staining with an anti-CD274 antibody. Bar, 100 μm. (b,c) Representative results of the anti-CD274 staining of clinical specimens obtained from 91 patients by surgical resection. CD274 immunohistochemistry was scored as described in Materials and Methods. Bar, 100 μm. (d) Kaplan–Meier analysis for the disease-specific survival rate of the two groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: CD274 expression in cholangiocarcinoma specimens and prognosis of cholangiocarcinoma patients. (a) Normal bile duct staining with an anti-CD274 antibody. Bar, 100 μm. (b,c) Representative results of the anti-CD274 staining of clinical specimens obtained from 91 patients by surgical resection. CD274 immunohistochemistry was scored as described in Materials and Methods. Bar, 100 μm. (d) Kaplan–Meier analysis for the disease-specific survival rate of the two groups.
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.

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