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

Albano Cáceres; Lorena Lobos-González; Rocío Bustos; América  Campos; Valeria Silva; Verónica Silva; Emanuel Jeldes; Carlos Salomon; Manuel Varas-Godoy; Eduardo Durán; Tamara Vera; Fernando Ezquer; Marcelo Ezquer; Verónica Bruzio; Jaime Villegas

doi:10.1038/s41598-019-57018-1

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

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

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	Spanish (Chile)
Journal	Scientific Reports
DOIs	https://doi.org/10.1038/s41598-019-57018-1
State	Published - 15 Jan 2020

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10.1038/s41598-019-57018-1

Cite this

Cáceres, A., Lobos-González, L., Bustos, R., Campos, A., Silva, V., Silva, V., Jeldes, E., Salomon, C., Varas-Godoy, M., Durán, E., Vera, T., Ezquer, F., Ezquer, M., Bruzio, V., & Villegas, J. (2020). Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells. Scientific Reports. https://doi.org/10.1038/s41598-019-57018-1

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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.",

keywords = "Extracellular vesicles, Tumor-growth, Prognostic-factor, Cadherin 5, Expression, Metastasis, Heterogeneity, Rnas, Microvesicles, Recurrence",

author = "Albano C{\'a}ceres and 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 Eduardo Dur{\'a}n and Tamara Vera and Fernando Ezquer and Marcelo Ezquer and Ver{\'o}nica Bruzio and Jaime Villegas",

year = "2020",

month = jan,

day = "15",

doi = "10.1038/s41598-019-57018-1",

language = "Espa{\~n}ol (Chile)",

journal = "Scientific Reports",

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Cáceres, A, Lobos-González, L, Bustos, R, Campos, A, Silva, V, Silva, V, Jeldes, E, Salomon, C, Varas-Godoy, M, Durán, E, Vera, T, Ezquer, F, Ezquer, M, Bruzio, V & Villegas, J 2020, 'Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells', Scientific Reports. https://doi.org/10.1038/s41598-019-57018-1

TY - JOUR

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

AU - Cáceres, Albano

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 - Durán, Eduardo

AU - Vera, Tamara

AU - Ezquer, Fernando

AU - Ezquer, Marcelo

AU - Bruzio, Verónica

AU - Villegas, Jaime

PY - 2020/1/15

Y1 - 2020/1/15

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.

AB - 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.

KW - Extracellular vesicles

KW - Tumor-growth

KW - Prognostic-factor

KW - Cadherin 5

KW - Expression

KW - Metastasis

KW - Heterogeneity

KW - Rnas

KW - Microvesicles

KW - Recurrence

U2 - 10.1038/s41598-019-57018-1

DO - 10.1038/s41598-019-57018-1

M3 - Artículo

SN - 2045-2322

JO - Scientific Reports

JF - Scientific Reports

ER -