title: Identification of tumor-initiating cells in a canine hepatocellular carcinoma cell line.
abstract: Tumor-initiating cells (TICs) or cancer stem cells (CSCs), a small subset of tumor cells, are involved in tumor initiation, progression, recurrence and metastasis. In human hepatocellular carcinoma (HCC), TICs are enriched with cell surface markers and have the ability to self-renew and differentiate tumors at a high frequency. We established a canine HCC cell line, HCC930599, and analyzed it for stem and progenitor cell marker expression using flow cytometry. HCC930599 showed high CD44 and CD29, moderate CD90, and low CD133, CD34, CD24, CD117, and CD13 expression. CD90(+)CD44(+) and CD90(-)CD44(+) cells were characterized using the in vitro sphere assay and an in vivo transplant model. CD90(+)CD44(+) cells acquired enhanced self-renewal capacity, proliferative activity and tumourigenicity compared with CD90(-)CD44(+) cells, suggesting that TICs exist in the HCC930599 cell line and that CD90 is a marker for enriched TICs. Understanding TIC characteristics may help elucidate hepatic carcinogenesis and HCC therapy development.
authors.affiliation: Department of Veterinary Pathology, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan. Electronic address: michishita@nvlu.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Michishita
authors.affiliation: Department of Veterinary Pathology, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Ezaki
authors.affiliation: Department of Pathology, School of Life and Environmental Science, Azabu University, 1-17-7 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan.
authors.forename: Kikumi
authors.initials: K
authors.lastname: Ogihara
authors.affiliation: Department of Pathology, School of Life and Environmental Science, Azabu University, 1-17-7 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Department of Veterinary Nursing, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Azakami
authors.affiliation: Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Department of Veterinary Biochemistry, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Arai
authors.affiliation: Laboratory of Veterinary Radiology, School of Veterinary Medicine, Azabu University, 1-17-7 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Shida
authors.affiliation: Department of Veterinary Pathology, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000662:veterinary*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D007150:Immunohistochemistry / Q000662:veterinary; D016130:Immunophenotyping / Q000379:methods / Q000662:veterinary; D008113:Liver Neoplasms / Q000473:pathology / Q000662:veterinary*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000473:pathology*; D018709:Statistics, Nonparametric
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor
keywords: Dog; Flow cytometry; Hepatocellular carcinoma; Tumor-initiating cells; Xenograft