Piskun Caroline M, Stein Timothy J
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Institute for Clinical & Translational Research, University of Wisconsin-Madison, Madison, WI, USA.
Vet Comp Oncol. 2016 Jun;14(2):e4-e16. doi: 10.1111/vco.12077. Epub 2013 Nov 21.
Canine osteosarcoma (OS) is an aggressive malignancy associated with poor outcomes. Therapeutic improvements are likely to develop from an improved understanding of signalling pathways contributing to OS development and progression. The Wnt signalling pathway is of interest for its role in osteoblast differentiation, its dysregulation in numerous cancer types, and the relative frequency of cytoplasmic accumulation of β-catenin in canine OS. This study aimed to determine the biological impact of inhibiting canonical Wnt signalling in canine OS, by utilizing either β-catenin siRNA or a dominant-negative T-cell factor (TCF) construct. There were no consistent, significant changes in cell line behaviour with either method compared to parental cell lines. Interestingly, β-catenin transcriptional activity was three-fold higher in normal canine primary osteoblasts compared to canine OS cell lines. These results suggest canonical Wnt signalling is minimally active in canine OS and its targeted inhibition is not a relevant therapeutic strategy.
犬骨肉瘤（OS）是一种侵袭性恶性肿瘤，预后较差。对促成骨肉瘤发生和发展的信号通路有更深入的了解可能会带来治疗上的改善。Wnt信号通路因其在成骨细胞分化中的作用、在多种癌症类型中的失调以及在犬骨肉瘤中β-连环蛋白在细胞质中积累的相对频率而受到关注。本研究旨在通过使用β-连环蛋白小干扰RNA（siRNA）或显性负性T细胞因子（TCF）构建体来确定抑制经典Wnt信号通路对犬骨肉瘤的生物学影响。与亲代细胞系相比，两种方法均未使细胞系行为发生一致、显著的变化。有趣的是，与犬骨肉瘤细胞系相比，正常犬原代成骨细胞中的β-连环蛋白转录活性高三倍。这些结果表明，经典Wnt信号通路在犬骨肉瘤中的活性极低，对其进行靶向抑制并非一种有效的治疗策略。
