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Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model

2020; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41598-020-63275-2

2045-2322

Flávio Lichtenstein, Asif Iqbal, Sonia Elisabete Alves de Lima Will, Rosemary Viola Bösch, Carlos DeOcesano-Pereira, Maurício Barbugiani Goldfeder, Roger Chammas, Carlos Eduardo Madureira Trufen, Kátia L.P. Morais, Jean Gabriel de Souza, Renato José Mendonça Natalino, Inácio L.M. Junqueira-de-Azevedo, Milton Yutaka Nishiyama, Úrsula Castro de Oliveira, F Alves, Jaqueline Mayara Araujo, Aline Ramos Maia Lobba, Ana Marisa Chudzinski‐Tavassi,

Heat shock proteins research

Abstract We have investigated Amblyomin-X-treated horse melanomas to better understand its mode of action through transcriptome analysis and the in vivo model. Amblyomin-X is a Kunitz-type homologous protein that selectively leads to the death of tumor cells via ER stress and apoptosis, currently under investigation as a new drug candidate for cancer treatment. Melanomas are immunogenic tumors, and a better understanding of the immune responses is warranted. Equine melanomas are spontaneous and not so aggressive as human melanomas are, as this study shows that the in vivo treatment of encapsulated horse melanoma tumors led to a significant reduction in the tumor size or even the complete disappearance of the tumor mass through intratumoral injections of Amblyomin-X. Transcriptome analysis identified ER- and mitochondria-stress, modulation of the innate immune system, apoptosis, and possibly immunogenic cell death activation. Interactome analysis showed that Amblyomin-X potentially interacts with key elements found in transcriptomics. Taken together, Amblyomin-X modulated the tumor immune microenvironment in different ways, at least contributing to induce tumor cell death.