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

Author(s):Show less -

Lichtenstein, Flavio ^{[1, 2]} ; Iqbal, Asif ^{[1, 2]} ; Alves de Lima Will, Sonia Elisabete ^{[1, 2]} ; Bosch, Rosemary Viola ^{[1, 2]} ; DeOcesano-Pereira, Carlos ^{[1, 2]} ; Goldfeder, Mauricio Barbugiani ^{[1, 2]} ; Chammas, Roger ^[3] ; Madureira Trufen, Carlos Eduardo ^{[1, 2]} ; Pereira Morais, Katia Luciano ^{[1, 2]} ; de Souza, Jean Gabriel ^{[1, 2]} ; Mendonca Natalino, Renato Jose ^[3] ; de Azevedo, Inacio Junqueira ^[4] ; Nishiyama Junior, Milton Yutaka ^[4] ; Oliveira, Ursula ^[4] ; Arruda Alves, Francisco Ivanio ^{[1, 2]} ; Araujo, Jaqueline Mayara ^{[1, 2]} ; Maia Lobba, Aline Ramos ^{[1, 2]} ; Chudzinski-Tavassi, Ana Marisa ^{[1, 2]}

Affiliation

^[1] Butantan Inst, Lab Mol Biol, Sao Paulo, SP - Brazil

^[2] Butantan Inst, Ctr Excellence New Target Discovery, CENTD, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ctr Translat Res Oncol, Inst Canc Estado Sao Paulo, ICESP, Fac Med, Sao Paulo - Brazil

^[4] Butantan Inst, Lab Especial Toxinol Aplicada CeTICS, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 APR 14 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 16/13588-4 - Revisiting cDNA libraries
• Grantee: Flavio Lichtenstein
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
• Grantee: Ana Marisa Chudzinski-Tavassi
• Support Opportunities: Research Grants - Applied Research Centers Program
• FAPESP's process: 17/02052-9 - Revisiting the cDNA library from Lonomia obliqua caterpillar to identify new molecular targets in inflammatory processes: bioinformatics, in vitro assays and transcriptomics
• Grantee: Jaqueline Mayara de Araujo
• Support Opportunities: Scholarships in Brazil - Scientific Initiation