Khammanivong A, Gorden B H, Frantz A M, Graef A J, Dickerson E B
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.
Vet Comp Oncol. 2016 Sep;14(3):e113-25. doi: 10.1111/vco.12114. Epub 2014 Aug 11.
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.
犬血管肉瘤是一种快速进展的疾病，对传统化疗反应不佳。尽管人们多次尝试推进治疗方案并改善治疗结果，但耐药性仍然是成功治疗的障碍。为了解决这个问题，我们使用了最近鉴定出的源自犬血管肉瘤细胞系并以非贴壁球体形式生长的祖细胞群体，以确定潜在的耐药机制以及耐药细胞群体。来自成球培养物的细胞对化疗药物表现出增强的抗性、拒染侧群的扩增以及ATP结合盒（ABC）转运蛋白表达的改变。侵袭研究表明细胞系之间以及球体和单层细胞群体之间存在差异。总体而言，我们的结果表明球体细胞群体包含不同的耐药细胞亚群，这些亚群利用多种机制逃避细胞毒性药物。我们的方法代表了一种研究血管肉瘤耐药性的新工具，这可能会改变这种疾病的治疗方法。
