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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: VETERINARY AND COMPARATIVE ONCOLOGY; v. 19, n. 3, p. 593-601, SEP 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/06217-5 - Desenvolvimento de um modelo para predição de neoantígenos MHC-I na espécie canina em células cancerosas
• Beneficiário: Pedro Ratto Lisboa Pires
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 19/05778-6 - Inibição combinada de proteínas BET e HDACs como uma estratégia efetiva para o tratamento do câncer de mama: um estudo comparativo
• Beneficiário: Pedro Luiz Porfirio Xavier
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 16/19307-7 - Caracterização de neoantígenos associados à transição epitélio-mesenquimal como potenciais alvos imunoterapêuticos
• Beneficiário: Pedro Ratto Lisboa Pires
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/06216-9 - Caracterização da atividade oncolítica do paramixovírus aviário sorotipo 1 em células de neoplasias mamárias de cadelas
• Beneficiário: Mariana Rodrigues dos Santos
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/02493-7 - Neoplasias mamárias de cadelas e a teoria das células-tronco cancerosas: uma abordagem comparada e translacional
• Beneficiário: Heidge Fukumasu
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores