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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
Authors:Federico Armando  Matteo Gambini  Attilio Corradi  Kathrin Becker  Katarzyna Marek  Vanessa Maria Pfankuche  Ahmed Elmonastir Mergani  Graham Brogden  Nicole de Buhr  Maren von Kckritz‐Blickwede  Hassan Y Naim  Wolfgang Baumgrtner  Christina Puff
Institution:Federico Armando,Matteo Gambini,Attilio Corradi,Kathrin Becker,Katarzyna Marek,Vanessa Maria Pfankuche,Ahmed Elmonastir Mergani,Graham Brogden,Nicole de Buhr,Maren von Köckritz‐Blickwede,Hassan Y. Naim,Wolfgang Baumgärtner,Christina Puff
Abstract: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.
Keywords:3D modelling  canine distemper virus  canine histiocytic sarcoma  DH82  mesenchymal to epithelial transition  viral oncolysis
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