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Scientific reports2020; 10(1); 6388; doi: 10.1038/s41598-020-63275-2

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

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.
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Publication Date: 2020-04-14 PubMed ID: 32286411PubMed Central: PMC7156751DOI: 10.1038/s41598-020-63275-2Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article investigates how Amblyomin-X, a protein currently under investigation for cancer treatment, affects melanomas in horses, resulting in tumor cell death. The study particularly sheds light on the effects of Amblyomin-X on stress, immunity, and cancer cell death and its potential as a novel cancer treatment candidate.

Introduction

  • This study discusses the effects of a drug candidate called Amblyomin-X on melanomas (a type of skin cancer) in horses.
  • Amblyomin-X is a Kunitz-type protein that selectively induces tumor cell death through endoplasmic reticulum (ER) stress and apoptosis (cell death).

Method

  • Scientists have used transcriptome analysis and in-vivo models to understand the mode of action of Amblyomin-X.
  • Equine melanomas, unlike human melanomas, are less aggressive and occur naturally, making them an ideal study model.
  • In this study, encapsulated horse melanoma tumors were treated with intratumoral injections of Amblyomin-X to observe the effects on tumor size and mass.

Findings

  • The treatment led to a significant shrinkage or even complete disappearance of the tumor mass, indicating effective tumor cell death.
  • Transcriptome analysis identified that Amblyomin-X induces ER and mitochondrial stress, orchestrates the innate immune system, and potentially activates immunogenic cell death.
  • Interactome analysis, which is the study of the entire set of molecular interactions in cells, demonstrated that Amblyomin-X potentially interacts with critical elements discovered in the transcriptome analysis

Conclusion

  • The study found that Amblyomin-X modulates the tumor immune microenvironment in various ways, contributing to tumor cell death.
  • These findings suggest that Amblyomin-X has the potential to be developed into a new drug treatment for cancer given its effect on stress, immunity, and cancer cell deaths.

Cite This Article

APA
Lichtenstein F, Iqbal A, de Lima Will SEA, Bosch RV, DeOcesano-Pereira C, Goldfeder MB, Chammas R, Trufen CEM, Morais KLP, de Souza JG, Natalino RJM, de Azevedo IJ, Nishiyama Junior MY, Oliveira U, Alves FIA, Araujo JM, Lobba ARM, Chudzinski-Tavassi AM. (2020). Modulation of stress and immune response by Amblyomin-X results in tumor cell death in a horse melanoma model. Sci Rep, 10(1), 6388. https://doi.org/10.1038/s41598-020-63275-2

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 10
Issue: 1
Pages: 6388

Researcher Affiliations

Lichtenstein, Flavio
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Iqbal, Asif
  • 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, Sonia Elisabete Alves
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Bosch, Rosemary Viola
  • 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, Carlos
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Goldfeder, Mauricio Barbugiani
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Chammas, Roger
  • 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, Carlos Eduardo Madureira
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Morais, Katia Luciano Pereira
  • 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, Jean Gabriel
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Natalino, Renato Jose Mendonça
  • 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, Inacio Junqueira
  • Laboratório Especial de Toxinologia Aplicada - CeTICS, Butantan Institute, São Paulo, Brazil.
Nishiyama Junior, Milton Yutaka
  • Laboratório Especial de Toxinologia Aplicada - CeTICS, Butantan Institute, São Paulo, Brazil.
Oliveira, Ursula
  • Laboratório Especial de Toxinologia Aplicada - CeTICS, Butantan Institute, São Paulo, Brazil.
Alves, Francisco Ivanio Arruda
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Araujo, Jaqueline Mayara
  • Laboratory of Molecular Biology, Butantan Institute, São Paulo, SP, Brazil.
  • CENTD, Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo, Brazil.
Lobba, Aline Ramos Maia
  • 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, Ana Marisa
  • 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.

MeSH Terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Arthropod Proteins / therapeutic use
  • Cell Death / drug effects
  • Drug Discovery
  • Horse Diseases / drug therapy
  • Horses
  • Male
  • Melanoma / drug therapy
  • Melanoma / veterinary
  • Salivary Proteins and Peptides / therapeutic use
  • Tumor Microenvironment / drug effects

Conflict of Interest Statement

The authors declare no competing interests.

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Citations

This article has been cited 9 times.
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