Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells

Lorena Lobos-González, Rocío Bustos, América Campos, Valeria Silva, Verónica Silva, Emanuel Jeldes, Carlos Salomon, Manuel Varas-Godoy, Albano Cáceres-Verschae, Eduardo Duran, Tamara Vera, Fernando Ezquer, Marcelo Ezquer, Verónica A. Burzio, Jaime Villegas

Resultado de la investigación: Article

Resumen

During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.

Idioma originalEnglish
Número de artículo343
PublicaciónScientific Reports
Volumen10
N.º1
DOI
EstadoPublished - 1 dic 2020

Huella dactilar

Exosomes
Antisense RNA
Untranslated RNA
Breast Neoplasms
mitochondrial RNA
Carcinoma
Neoplasms
Antisense Oligonucleotides
Proteomics
Cause of Death
Carcinogenesis
Proteins
Apoptosis
Neoplasm Metastasis

ASJC Scopus subject areas

  • General

Citar esto

Lobos-González, Lorena ; Bustos, Rocío ; Campos, América ; Silva, Valeria ; Silva, Verónica ; Jeldes, Emanuel ; Salomon, Carlos ; Varas-Godoy, Manuel ; Cáceres-Verschae, Albano ; Duran, Eduardo ; Vera, Tamara ; Ezquer, Fernando ; Ezquer, Marcelo ; Burzio, Verónica A. ; Villegas, Jaime. / Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells. En: Scientific Reports. 2020 ; Vol. 10, N.º 1.
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title = "Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells",
abstract = "During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.",
author = "Lorena Lobos-Gonz{\'a}lez and Roc{\'i}o Bustos and Am{\'e}rica Campos and Valeria Silva and Ver{\'o}nica Silva and Emanuel Jeldes and Carlos Salomon and Manuel Varas-Godoy and Albano C{\'a}ceres-Verschae and Eduardo Duran and Tamara Vera and Fernando Ezquer and Marcelo Ezquer and Burzio, {Ver{\'o}nica A.} and Jaime Villegas",
year = "2020",
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doi = "10.1038/s41598-019-57018-1",
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Lobos-González, L, Bustos, R, Campos, A, Silva, V, Silva, V, Jeldes, E, Salomon, C, Varas-Godoy, M, Cáceres-Verschae, A, Duran, E, Vera, T, Ezquer, F, Ezquer, M, Burzio, VA & Villegas, J 2020, 'Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells', Scientific Reports, vol. 10, n.º 1, 343. https://doi.org/10.1038/s41598-019-57018-1

Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells. / Lobos-González, Lorena; Bustos, Rocío; Campos, América; Silva, Valeria; Silva, Verónica; Jeldes, Emanuel; Salomon, Carlos; Varas-Godoy, Manuel; Cáceres-Verschae, Albano; Duran, Eduardo; Vera, Tamara; Ezquer, Fernando; Ezquer, Marcelo; Burzio, Verónica A.; Villegas, Jaime.

En: Scientific Reports, Vol. 10, N.º 1, 343, 01.12.2020.

Resultado de la investigación: Article

TY - JOUR

T1 - Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells

AU - Lobos-González, Lorena

AU - Bustos, Rocío

AU - Campos, América

AU - Silva, Valeria

AU - Silva, Verónica

AU - Jeldes, Emanuel

AU - Salomon, Carlos

AU - Varas-Godoy, Manuel

AU - Cáceres-Verschae, Albano

AU - Duran, Eduardo

AU - Vera, Tamara

AU - Ezquer, Fernando

AU - Ezquer, Marcelo

AU - Burzio, Verónica A.

AU - Villegas, Jaime

PY - 2020/12/1

Y1 - 2020/12/1

N2 - During intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.

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