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Article

Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma

1
Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany
2
Department of Veterinary Medicine, An-Najah National University, 9720061 Nablus, Palestine
3
Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Straße 1, 30625 Hannover, Germany
4
Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Bünteweg 2, 30559 Hannover, Germany
5
Dipartimento di Medicina Veterinaria (DIMEVET), Università degli Studi di Milano, Via dell’Università 6, 26900 Lodi, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work and are listed in alphabetical order.
Academic Editor: Laura Menotti
Int. J. Mol. Sci. 2021, 22(7), 3578; https://doi.org/10.3390/ijms22073578
Received: 5 March 2021 / Revised: 24 March 2021 / Accepted: 26 March 2021 / Published: 30 March 2021
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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. View Full-Text
Keywords: canine distemper virus; canine histiocytic sarcoma; microvessel density; murine xenograft model; oncolytic virus; tumor microenvironment canine distemper virus; canine histiocytic sarcoma; microvessel density; murine xenograft model; oncolytic virus; tumor microenvironment
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MDPI and ACS Style

Armando, F.; Fayyad, A.; Arms, S.; Barthel, Y.; Schaudien, D.; Rohn, K.; Gambini, M.; Lombardo, M.S.; Beineke, A.; Baumgärtner, W.; Puff, C. Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma. Int. J. Mol. Sci. 2021, 22, 3578. https://doi.org/10.3390/ijms22073578

AMA Style

Armando F, Fayyad A, Arms S, Barthel Y, Schaudien D, Rohn K, Gambini M, Lombardo MS, Beineke A, Baumgärtner W, Puff C. Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma. International Journal of Molecular Sciences. 2021; 22(7):3578. https://doi.org/10.3390/ijms22073578

Chicago/Turabian Style

Armando, Federico, Adnan Fayyad, Stefanie Arms, Yvonne Barthel, Dirk Schaudien, Karl Rohn, Matteo Gambini, Mara S. Lombardo, Andreas Beineke, Wolfgang Baumgärtner, and Christina Puff. 2021. "Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma" International Journal of Molecular Sciences 22, no. 7: 3578. https://doi.org/10.3390/ijms22073578

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