title: SSEA-3 as a novel amplifying cancer cell surface marker in colorectal             cancers.
abstract: Findings from studies on stem cells have been applied to cancer stem cell (CSC) research, but little is known about the relationship between ES cell-related cell surface markers and CSCs. In this study, we focused on stage-specific embryonic antigen 3 (SSEA-3), a marker of mesenchymal stem cells and Muse cells in colorectal cancer (CRC). Expression of SSEA-3 in human CRC cell lines and clinical specimens, specifically the relationship of SSEA-3 expression and the representative CSC markers (CD44, CD166, ALDH, CD24 and CD26) as well as with mesenchymal stem cell/Muse cell marker (CD105) were assessed. To characterize SSEA-3-expressing cells, tumorigenicity, sphere formation ability, expression of iPS genes (Oct4, NANOG, SOX2 and c-Myc), cell proliferation and cell cycle status were assessed. SSEA-3 expression was identified in Caco-2, DLD-1, HT-29, SW480 and HCT116, but not in CaR-1 cells. No significant relationship between SSEA-3 and other stem cell markers was detected. SSEA-3+ cells showed increased tumorigenicity in vivo, but lower sphere formation ability in vitro than SSEA-3-. iPS gene expression was not correlated with SSEA-3 expression status. SSEA-3+ cells showed higher proliferative ability than SSEA-3- through enhanced cell cycles by decreased expression of p21Cip1/Waf1 and p27Kip1. Immunofluorescence analysis in clinical specimens indicated that expression of SSEA-3 is limited to stromal cells in normal mucosa but broad in poorly differentiated adenocarcinoma. These observations indicated that SSEA-3+ cells in CRC have immature phenotype but decreased self-renewal ability and may function as tumor transient amplifying cells or delayed contributing tumor-initiating cells.
authors.affiliation: Department of Gastroenterological Surgery, Osaka University, Suita, Osaka, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D055746:Stage-Specific Embryonic Antigens; C052924:stage-specific embryonic antigen-3