Enhanced expression of cancer testis antigen genes in glioma stem cells.
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.
Yawata
Toshio
T
Department of Neurosurgery, Kochi Medical School, Nankoku, Kochi, Japan.
Nakai
Eiichi
E
Park
Kae Chang
KC
Chihara
Takahiro
T
Kumazawa
Ayano
A
Toyonaga
Shinichi
S
Masahira
Takanori
T
Nakabayashi
Hiromichi
H
Kaji
Takao
T
Shimizu
Keiji
K
D000107:Acetylation; D000368:Aged; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D005910:Glioma / Q000235:genetics* / Q000276:immunology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D000951:Antigens, Neoplasm; D006657:Histones; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins