scholarly journals Mesenchymal to epithelial transition driven by canine distemper virus infection of canine histiocytic sarcoma cells contributes to a reduced cell motility in vitro

2020 ◽  
Vol 24 (16) ◽  
pp. 9332-9348 ◽  
Author(s):  
Federico Armando ◽  
Matteo Gambini ◽  
Attilio Corradi ◽  
Kathrin Becker ◽  
Katarzyna Marek ◽  
...  
2021 ◽  
Vol 22 (7) ◽  
pp. 3578
Author(s):  
Federico Armando ◽  
Adnan Fayyad ◽  
Stefanie Arms ◽  
Yvonne Barthel ◽  
Dirk Schaudien ◽  
...  

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.


Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 200 ◽  
Author(s):  
Federico Armando ◽  
Matteo Gambini ◽  
Attilio Corradi ◽  
Chiara Giudice ◽  
Vanessa Maria Pfankuche ◽  
...  

Histiocytic sarcomas represent malignant tumors which require new treatment strategies. Canine distemper virus (CDV) is a promising candidate due to its oncolytic features reported in a canine histiocytic sarcoma cell line (DH82 cells). Interestingly, the underlying mechanism might include a dysregulation of angiogenesis. Based on these findings, the aim of the present study was to investigate the impact of a persistent CDV-infection on oxidative stress mediated changes in the expression of hypoxia-inducible factor (HIF)-1α and its angiogenic downstream pathway in DH82 cells in vitro. Microarray data analysis, immunofluorescence for 8-hydroxyguanosine, superoxide dismutase 2 and catalase, and flow cytometry for oxidative burst displayed an increased oxidative stress in persistently CDV-infected DH82 cells (DH82Ond pi) compared to controls. The HIF-1α expression in DH82Ond pi increased, as demonstrated by Western blot, and showed an unexpected, often sub-membranous distribution, as shown by immunofluorescence and immunoelectron microscopy. Furthermore, microarray data analysis and immunofluorescence confirmed a reduced expression of VEGF-B in DH82Ond pi compared to controls. In summary, these results suggest a reduced activation of the HIF-1α angiogenic downstream pathway in DH82Ond pi cells in vitro, most likely due to an excessive, unusually localized, and non-functional expression of HIF-1α triggered by a CDV-induced increased oxidative stress.


1987 ◽  
Vol 74 (4) ◽  
pp. 366-373 ◽  
Author(s):  
A. Zurbriggen ◽  
M. Vandevelde ◽  
M. Dumas ◽  
C. Griot ◽  
E. Bollo

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Xianghong Xue ◽  
Yelei Zhu ◽  
Lina Yan ◽  
Gary Wong ◽  
Peilu Sun ◽  
...  

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