Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines

Author(s)

Santos, Mariana Rodrigues ^[1] ; Porfirio Xavier, Pedro Luiz ^[1] ; Lisboa Pires, Pedro Ratto ^[1] ; Rochetti, Arina Lazaro ^[1] ; Rosim, Daniele Fernanda ^[1] ; Scagion, Guilherme Pereira ^[1] ; Pires de Campos Zuccari, Debora Aparecida ^[2] ; Munir, Muhammad ^[3] ; Ferreira, Helena Lage ^[1] ; Fukumasu, Heidge ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Anim Sci & Food Engn, Dept Vet Med, Av Duque de Caxias Norte 225, Pirassununga, SP - Brazil

^[2] Fac Med Sao Jose do Rio Preto FAMERP, Dept Mol Biol, Lab Mol Invest Canc LIMC, Sao Jose Do Rio Preto - Brazil

^[3] Univ Lancaster, Div Biomed & Life Sci, Lancaster - England

• Document type: Journal article
• Source: VETERINARY AND COMPARATIVE ONCOLOGY; v. 19, n. 3, p. 593-601, SEP 2021.
• Web of Science Citations: 0

Abstract

Canine mammary carcinoma (CMC) is one of the major health threats in dogs. The oncolytic virotherapy is a promising strategy to treat canine as well as human cancer patients with non-pathogenic replicating viruses. Here, we evaluated the antitumor activity of one lentogenic, non-lytic Newcastle disease virus (NDV) LaSota strain expressing GFP (NDV-GFP) on five different CMCs and one non-tumorigenic cell line, regarding cell viability, cell death, selectivity index, morphology, global and target gene expression analysis. As evidenced by the selectivity index, all CMC cell lines were more susceptible to NDV-GFP in comparison with the non-tumorigenic cells (similar to 3.1x to similar to 78.7x). In addition, the oncolytic effect of NDV-GFP was more evident in more malignant CMC cells. Also, we observed an inverse association of the IFN pathway expression and the susceptibility to NDV. The downregulated genes in NDV-GFP-sensitive cells were functionally enriched for antiviral mechanisms by interferon and immune system pathways, demonstrating that these mechanisms are the most prominent for oncolysis by NDV. To our knowledge, this is the first description of oncolysis by an NDV strain in canine mammary cancer cells. We also demonstrated specific molecular pathways related to NDV susceptibility in these cancer cells, opening the possibility to use NDV as a therapeutic-targeted option for more malignant CMCs. Therefore, these results urge for more studies using oncolytic NDVs, especially considering genetic editing to improve efficacy in dogs. (AU)

• FAPESP's process: 18/06217-5 - Development of a Canine MHC-I neoantigen prediction model in cancer cells
• Grantee: Pedro Ratto Lisboa Pires
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 19/05778-6 - Combined inhibition of BET proteins AND HDACs as an effective strategy for the treatment of mammary cancer: a comparative study
• Grantee: Pedro Luiz Porfirio Xavier
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/19307-7 - Characterization of neoantigens associated to epithelial-mesenchymal transition as potential immunotherapeutic targets
• Grantee: Pedro Ratto Lisboa Pires
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/06216-9 - Characterization of the oncolytic activity of avian paramyxovirus serotype 1 in mammary cancer cells of female dogs
• Grantee: Mariana Rodrigues dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/02493-7 - Mammary tumors of dogs and the cancer stem cell theory: a comparative and translational approach
• Grantee: Heidge Fukumasu
• Support Opportunities: Research Grants - Young Investigators Grants