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Identification of tumor-initiating cells in a canine hepatocellular carcinoma cell line
Authors:Masaki Michishita  Shiori Ezaki  Kikumi Ogihara  Yuko Naya  Daigo Azakami  Takayuki Nakagawa  Nobuo Sasaki  Toshiro Arai  Takuo Shida  Kimimasa Takahashi
Institution:1. Department of Veterinary Pathology, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan;2. Department of Pathology, School of Life and Environmental Science, Azabu University, 1-17-7 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan;3. Department of Veterinary Nursing, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan;4. Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan;5. Department of Veterinary Biochemistry, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan;6. Laboratory of Veterinary Radiology, School of Veterinary Medicine, Azabu University, 1-17-7 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan
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 CD90CD44+ 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 CD90CD44+ 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.
Keywords:Dog  Flow cytometry  Hepatocellular carcinoma  Tumor-initiating cells  Xenograft
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