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

Autor: Lichtenstein F; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Iqbal A; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., de Lima Will SEA; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Bosch RV; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., DeOcesano-Pereira C; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Goldfeder MB; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Chammas R; ICESP, Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Trufen CEM; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Morais KLP; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., de Souza JG; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Natalino RJM; ICESP, Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., de Azevedo IJ; Laboratório Especial de Toxinologia Aplicada - CeTICS, Butantan Institute, São Paulo, Brazil., Nishiyama Junior MY; Laboratório Especial de Toxinologia Aplicada - CeTICS, Butantan Institute, São Paulo, Brazil., Oliveira U; Laboratório Especial de Toxinologia Aplicada - CeTICS, Butantan Institute, São Paulo, Brazil., Alves FIA; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Araujo JM; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Lobba ARM; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil., Chudzinski-Tavassi AM; Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil. ana.chudzinski@butantan.gov.br.; CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil. ana.chudzinski@butantan.gov.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Apr 14; Vol. 10 (1), pp. 6388. Date of Electronic Publication: 2020 Apr 14.
DOI: 10.1038/s41598-020-63275-2
Abstrakt: 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.
Databáze: MEDLINE
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