title: Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines.
abstract: There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44+CD24- population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 1 × 10(4)sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis.
authors.affiliation: Department of Veterinary Pathology, Nippon Veterinary and Life Science University, 1-7-1 Kyounan-cho, Musashino, Tokyo 180-8602, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Michishita
authors.forename: Rui
authors.initials: R
authors.lastname: Akiyoshi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yoshimura
authors.forename: Takuo
authors.initials: T
authors.lastname: Katsumoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Kozo
authors.initials: K
authors.lastname: Ohkusu-Tsukada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D019450:Genes, MDR; D006023:Glycoproteins / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D010455:Peptides / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D015854:Up-Regulation
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D010455:Peptides; C000606024:Prom1 protein, mouse; D051880:Receptors, Notch; D004317:Doxorubicin