Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respondpoorly to conventional treatment approaches. Oncolytic viruses, which have gained significanttraction as a cancer therapy in recent decades, represent a promising option for treating histiocyticsarcomas through their replication and/or by modulating the tumor microenvironment. The liveattenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractivecandidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV wasused to investigate the impact of this virus infection on tumor cell growth through direct oncolyticeffects or by virus-mediated modulation of the tumor microenvironment with special emphasis onangiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in amurine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplantedcanine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompaniedby necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesisand modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibitstumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis andmodulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its rolein oncolytic therapies

Title

International Journal of Molecular Sciences

Publisher

MDPI

Publisher Country

Switzerland

Indexing

Thomson Reuters

Impact Factor

4.556

Publication Type

Both (Printed and Online)

Volume

22

Year

2021

Pages

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