Rights statement: This is the peer reviewed version of the following article: Santos, MR, Xavier, PLP, Pires, PRL, et al. Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines. Vet Comp Oncol. 2021; 19: 593– 601. doi.org/10.1111/vco.12699 which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1111/vco.12699 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
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Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines
AU - Santos, Mariana Rodrigues
AU - Xavier, Pedro Luiz Porfírio
AU - Pires, Pedro Ratto Lisboa
AU - Rochetti, Arina Lázaro
AU - Rosim, Daniele Fernanda
AU - Scagion, Guilherme Pereira
AU - Zuccari, Debora Aparecida Pires Campos
AU - Munir, Muhammad
AU - Ferreira, Helena Lage
AU - Fukumasu, Heidge
N1 - This is the peer reviewed version of the following article: Santos, MR, Xavier, PLP, Pires, PRL, et al. Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines. Vet Comp Oncol. 2021; 19: 593– 601. doi.org/10.1111/vco.12699 which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1111/vco.12699 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
PY - 2021/9/30
Y1 - 2021/9/30
N2 - 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 (~3.1× to ~78.7×). 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.
AB - 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 (~3.1× to ~78.7×). 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.
KW - Comparative oncology
KW - IFN-β
KW - Paramyxovirus
KW - RNA-seq
KW - Selectivity index
U2 - 10.1111/vco.12699
DO - 10.1111/vco.12699
M3 - Journal article
VL - 19
SP - 593
EP - 601
JO - Veterinary and Comparative Oncology
JF - Veterinary and Comparative Oncology
IS - 3
ER -