Oncolytic reovirus in canine mast cell tumor.

Oncolytic reovirus in canine mast cell tumor.
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DOI:
10.1371/journal.pone.0073555
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Mizuno T
Mizuno T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hwang CC;Umeki S;Kubo M;Hayashi T;Shimoda H;Mochizuki M;Maeda K;Baba K;Hiraoka H;Coffey M;Okuda M;Mizuno T

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呼肠孤病毒的使用已经达到了人类癌症的第二和第三阶段临床试验。然而,这是第一次报道呼肠孤病毒在兽医肿瘤学中的溶瘤作用,重点是犬肥大细胞瘤(MCT),这是狗最常见的皮肤肿瘤。由于人类和犬类癌症有许多相似之处,我们假设呼肠孤病毒的溶瘤作用可以在犬类癌症中得到利用。本研究的目的是研究呼肠孤病毒对犬MCT的体外、体内和体外溶瘤作用。我们证明MCT细胞系对呼肠孤病毒高度敏感,这表明细胞显著死亡,后代病毒产量高,病毒复制。呼肠孤病毒可诱导犬MCT细胞发生凋亡,但与其RAS激活状态无关。体内研究采用单侧和双侧MCT皮下移植模型,肿瘤内单一呼肠孤病毒治疗,肿瘤质量明显减少。此外,呼肠孤病毒可在原代犬MCT标本中诱导细胞死亡。然而,犬和小鼠骨髓来源的肥大细胞(BMCMC)也对呼肠孤病毒敏感。这些结果的结合支持呼肠孤病毒作为治疗犬MCT的潜在价值,但值得进一步研究呼肠孤病毒易感性的决定因素。
The usage of reovirus has reached phase II and III clinical trials in human cancers. However, this is the first study to report the oncolytic effects of reovirus in veterinary oncology, focusing on canine mast cell tumor (MCT), the most common cutaneous tumor in dogs. As human and canine cancers share many similarities, we hypothesized that the oncolytic effects of reovirus can be exploited in canine cancers. The objective of this study was to determine the oncolytic effects of reovirus in canine MCT in vitro, in vivo and ex vivo. We demonstrated that MCT cell lines were highly susceptible to reovirus as indicated by marked cell death, high production of progeny virus and virus replication. Reovirus induced apoptosis in the canine MCT cell lines with no correlation to their Ras activation status. In vivo studies were conducted using unilateral and bilateral subcutaneous MCT xenograft models with a single intratumoral reovirus treatment and apparent reduction of tumor mass was exhibited. Furthermore, cell death was induced by reovirus in primary canine MCT samples in vitro. However, canine and murine bone marrow-derived mast cells (BMCMC) were also susceptible to reovirus. The combination of these results supports the potential value of reovirus as a therapy in canine MCT but warrants further investigation on the determinants of reovirus susceptibility.
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