title: High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.
abstract: Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan ; Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Emori
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan ; Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Murase
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan ; Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan ; Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Kochin
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kaya
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagoya
authors.affiliation: Department of Orthopedic Surgery, Fukuoka University School of Medicine, Nanakuma, Jonan Ward, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nishio
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine, Nanakuma, Jonan Ward, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.affiliation: Department of Public Health, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sonoda
authors.affiliation: Department of Surgical Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Wada
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000328:Adult; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D058851:GPI-Linked Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C120523:CD109 protein, human; D017931:DNA Primers; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase