TY - JOUR
T1 - Enhanced expression of cancer testis antigen genes in glioma stem cells
AU - Yawata, Toshio
AU - Nakai, Eiichi
AU - Park, Kae Chang
AU - Chihara, Takahiro
AU - Kumazawa, Ayano
AU - Toyonaga, Shinichi
AU - Masahira, Takanori
AU - Nakabayashi, Hiromichi
AU - Kaji, Takao
AU - Shimizu, Keiji
PY - 2010/6
Y1 - 2010/6
N2 - Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients.
AB - Cancer stem cells are an important target for effective therapy, since they show tumorigenicity, chemoresistance, and radioresistance. We isolated cancer stem cells from glioma cell lines and tissues and examined the expression of cancer testis antigen (CTA) genes as potential target molecules for cancer vaccine therapy. CTA genes were highly and frequently expressed in cancer stem cells compared with differentiated cells. In addition, histone acetylation levels in the promoter regions of CTA genes were high in cancer stem cells and low in differentiated cells, while DNA methylation analysis of the promoter regions revealed hypomethylation in cancer stem cells. This epigenetic difference between cells leads to heterogeneous expression of CTA genes in the tumor mass, which consists of cells at various levels of differentiation. Moreover, the expression level of HLA class I antigens was not affected by the differentiation status, suggesting that CTA genes may present as surface antigens in cancer stem cells. Taken together, these findings suggest that CTA genes may be attractive candidates for targeted vaccine therapy against cancer stem cells in glioma patients.
KW - Cancer stem cells
KW - Cell differentiation
KW - Epigenetics
UR - http://www.scopus.com/inward/record.url?scp=77952499771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952499771&partnerID=8YFLogxK
U2 - 10.1002/mc.20614
DO - 10.1002/mc.20614
M3 - Article
C2 - 20082319
AN - SCOPUS:77952499771
VL - 49
SP - 532
EP - 544
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 6
ER -
