title: Canine osteosarcoma cell lines contain stem-like cancer cells: biological and pharmacological characterization.
abstract: Cancer stem cells (CSCs) represent a small subpopulation of cells responsible for tumor formation and progression, drug resistance, tumor recurrence and metastasization. CSCs have been identified in many human tumors including osteosarcoma (OSA). CSC distinctive properties are the expression of stem cell markers, sustained growth, self-renewal and tumorigenicity. Here we report the isolation of stem-like cells from two canine OSA cultures, characterized by self-renewal, evaluated by sphere formation ability, differential marker expression, and in vitro proliferation when cultured in a medium containing EGF and bFGF. Current therapies for OSA increased survival time, but prognosis remains poor, due to the development of drug resistance and metastases. Chemotherapy shrinks the tumor mass but CSCs remain unaffected, leading to tumor recurrence. Metformin, a drug for type 2 diabetes, has been shown to possess antitumor properties affecting CSC survival in different human and animal cancers. Here we show that metformin has a significant antiproliferative effect on canine OSA stem-like cells, validating this in vitro model for further pre-clinical drug evaluations. In conclusion, our results demonstrate the feasibility of obtaining CSC-enriched cultures from primary canine OSA cells as a promising model for biological and pharmacological studies of canine and human OSAs.
authors: Monica
authors: M
authors: Gatti
authors: Roberto
authors: R
authors: Wurth
authors: Guendalina
authors: G
authors: Vito
authors: Alessandra
authors: A
authors: Pattarozzi
authors: Chiara
authors: C
authors: Campanella
authors: Stefano
authors: S
authors: Thellung
authors: Lorella
authors: L
authors: Maniscalco
authors: Raffaella
authors: R
authors: De Maria
authors: Valentina
authors: V
authors: Villa
authors: Alessandro
authors: A
authors: Corsaro
authors: Mario
authors: M
authors: Nizzari
authors: Adriana
authors: A
authors: Bajetto
authors: Alessandra
authors: A
authors: Ratto
authors: Angelo
authors: A
authors: Ferrari
authors: Federica
authors: F
authors: Barbieri
authors: Tullio
authors: T
authors: Florio
mesh_terms: D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000502:physiology*; D012516:Osteosarcoma / Q000662:veterinary*
chemical_list: D015415:Biomarkers