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Oxidative stress in canine histiocytic sarcoma cells (DH82 cells) induced by a persistent canine distemper virus infection leads to impairment of the HIF-1α downstream pathway in vitro
Introduction Histiocytic sarcoma (HS) is a highly aggressive neoplasm with a limited response to therapies. A promising new approach might be oncolytic virotherapy. Angiogenesis is essential for tumor growth and metastasis. One of the key regulator factors for angiogenesis is hypoxia inducible factor-1α (HIF-1α). In addition, angiogenesis is regulated by reactive oxygen species (ROS). The aim of this study was to evaluate the influence of canine distemper virus (CDV) infection on HIF-1α expression in canine HS cells (DH82 cells).
Materials and methods Non-infected and persistently CDV infected DH82 cells were investigated in vitro. The expression of oxidative stress and angiogenesis markers were evaluated on a molecular and protein level using microarray data, immunofluorescence microscopy, Western blot and flow cytometry.
Results Persistently CDV-infected DH82 cells displayed an increased oxidative stress due to viral infection that leads to a dysregulated HIF-1α expression with a consecutive downregulation of the downstream angiogenetic pathway.
Conclusion These results indicate that a persistent CDV-infection seems to affect the HIF-1α pathway resulting in a decrease in the downstream production of angiogenetic factors in vitro.
Article published online:
08 July 2020
© Georg Thieme Verlag KG
Stuttgart · New York