title: Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells.
abstract: The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding β-1,3-galactosyltransferase 5 (β3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan;
authors.forename: Sarah K C
authors.initials: SK
authors.lastname: Cheung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute of Basic Medical Science, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Po-Kai
authors.initials: PK
authors.lastname: Chuang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Han-Wen
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Hwang-Verslues
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Candy Hsin-Hua
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Yang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Shen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.affiliation: Institute of Basic Medical Science, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chuan-Fa
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; chwong@gate.sinica.edu.tw.
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis*; D017209:Apoptosis; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005700:Galactosyltransferases / Q000032:analysis*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D055746:Stage-Specific Embryonic Antigens / Q000032:analysis*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D055746:Stage-Specific Embryonic Antigens; C052924:stage-specific embryonic antigen-3; C479886:B3GALT5 protein, human; D005700:Galactosyltransferases
keywords: cancer-specific; globo-series; glycolipids