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Mesenchymal to epithelial transition driven by canine distemper virus infection of canine histiocytic sarcoma cells contributes to a reduced cell motility in vitro.
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2020-07-06 , DOI: 10.1111/jcmm.15585
Federico Armando 1, 2 , Matteo Gambini 1, 3 , Attilio Corradi 2 , Kathrin Becker 1 , Katarzyna Marek 1 , Vanessa Maria Pfankuche 1 , Ahmed Elmonastir Mergani 4 , Graham Brogden 4, 5 , Nicole de Buhr 4 , Maren von Köckritz-Blickwede 4, 6 , Hassan Y Naim 4 , Wolfgang Baumgärtner 1 , Christina Puff 1
Affiliation  

Sarcomas especially of histiocytic origin often possess a poor prognosis and response to conventional therapies. Interestingly, tumours undergoing mesenchymal to epithelial transition (MET) are often associated with a favourable clinical outcome. This process is characterized by an increased expression of epithelial markers leading to a decreased invasion and metastatic rate. Based on the failure of conventional therapies, viral oncolysis might represent a promising alternative with canine distemper virus (CDV) as a possible candidate. This study hypothesizes that a CDV infection of canine histiocytic sarcoma cells (DH82 cells) triggers the MET process leading to a decreased cellular motility. Immunofluorescence and immunoblotting were used to investigate the expression of epithelial and mesenchymal markers followed by scratch assay and an invasion assay as functional confirmation. Furthermore, microarray data were analysed for genes associated with the MET process, invasion and angiogenesis. CDV‐infected cells exhibited an increased expression of epithelial markers such as E‐cadherin and cytokeratin 8 compared to controls, indicating a MET process. This was accompanied by a reduced cell motility and invasiveness. Summarized, these results suggest that CDV infection of DH82 cells triggers the MET process by an increased expression of epithelial markers resulting in a decreased cell motility in vitro.

中文翻译:

由犬瘟热病毒感染犬组织细胞肉瘤细胞驱动的间充质到上皮转化有助于降低体外细胞运动。

肉瘤,尤其是组织细胞来源的肉瘤,通常预后较差,对常规疗法的反应也很差。有趣的是,经历间充质到上皮转化 (MET) 的肿瘤通常与良好的临床结果相关。该过程的特征在于上皮标志物的表达增加,导致侵袭和转移率降低。基于常规疗法的失败,病毒溶瘤可能是一种有希望的替代方法,犬瘟热病毒 (CDV) 可能是候选者。该研究假设犬组织细胞肉瘤细胞(DH82 细胞)的 CDV 感染触发 MET 过程,导致细胞运动性降低。使用免疫荧光和免疫印迹研究上皮和间充质标记物的表达,然后进行划痕试验和侵袭试验作为功能确认。此外,分析了与 MET 过程、侵袭和血管生成相关的基因的微阵列数据。与对照相比,CDV 感染的细胞表现出上皮标志物(如 E-钙粘蛋白和细胞角蛋白 8)的表达增加,表明存在 MET 过程。这伴随着细胞运动性和侵袭性的降低。总之,这些结果表明 DH82 细胞的 CDV 感染通过增加上皮标志物的表达触发 MET 过程,导致体外细胞运动性降低。侵袭和血管生成。与对照相比,CDV 感染的细胞表现出上皮标志物(如 E-钙粘蛋白和细胞角蛋白 8)的表达增加,表明存在 MET 过程。这伴随着细胞运动性和侵袭性的降低。总之,这些结果表明 DH82 细胞的 CDV 感染通过增加上皮标志物的表达触发 MET 过程,导致体外细胞运动性降低。侵袭和血管生成。与对照相比,CDV 感染的细胞表现出上皮标志物(如 E-钙粘蛋白和细胞角蛋白 8)的表达增加,表明存在 MET 过程。这伴随着细胞运动性和侵袭性的降低。总之,这些结果表明 DH82 细胞的 CDV 感染通过增加上皮标志物的表达触发 MET 过程,导致体外细胞运动性降低。
更新日期:2020-08-11
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