Stiftung Tierärztliche Hochschule Hannover (TiHo)

Oxidative stress in canine histiocytic sarcoma cells induced by an infection with canine distemper virus led to a dysregulation of HIF-1α downstream pathway resulting in a reduced expression of VEGF-B in vitro

Armando, Federico ORCID; Gambini, Matteo ORCID; Corradi, Attilio ORCID; Giudice, Chiara; Pfankuche, Vanessa Maria GND; Brogden, Graham GND; Attig, Friederike; von Köckritz-Blickwede, Maren; Baumgärtner, Wolfgang ORCID; Puff, Christina GND

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.

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Armando, F., Gambini, M., Corradi, A., Giudice, C., Pfankuche, V.M., Brogden, G., Attig, F., von Köckritz-Blickwede, M., Baumgärtner, W., Puff, C., 2020. Oxidative stress in canine histiocytic sarcoma cells induced by an infection with canine distemper virus led to a dysregulation of HIF-1α downstream pathway resulting in a reduced expression of VEGF-B in vitro. Viruses 12. https://doi.org/10.3390/v12020200
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