title: Identification of drug-resistant subpopulations in canine hemangiosarcoma.
abstract: Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug-resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Khammanivong
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Gorden
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Frantz
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Graef
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Dickerson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D019008:Drug Resistance, Neoplasm; D006394:Hemangiosarcoma / Q000378:metabolism / Q000662:veterinary*
keywords: ABC transporter; canine; drug resistance; hemangiosarcoma; side population
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