Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs

Lavinia Raimondi, Angela De Luca, Alessia Gallo, Viviana Costa, Giovanna Russelli, Nicola Cuscino, Mauro Manno, Samuele Raccosta, Valeria Carina, Daniele Bellavia, Alice Conigliaro, Riccardo Alessandro, Milena Fini, Pier Giulio Conaldi, Gianluca Giavaresi

Research output: Contribution to journalArticle

Abstract

Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodelling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the miRNA cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and Huvec cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment, also by a specific packaging of miRNAs.

Original languageEnglish
JournalCarcinogenesis
DOIs
Publication statusE-pub ahead of print - Jul 10 2019

Fingerprint

Exosomes
Tumor Microenvironment
Product Packaging
Osteosarcoma
MicroRNAs
RNA Sequence Analysis
Biological Phenomena
Neoplasms
Bone Remodeling
Osteoclasts
Bone Resorption
Computational Biology
Cell Communication
Cluster Analysis
Carcinogenesis
Endothelial Cells
Neoplasm Metastasis
Bone and Bones
Growth

Keywords

  • exosomes
  • microRNAs profiling
  • osteosarcoma
  • tumor microenvironment

Cite this

Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs. / Raimondi, Lavinia; De Luca, Angela; Gallo, Alessia; Costa, Viviana; Russelli, Giovanna; Cuscino, Nicola; Manno, Mauro; Raccosta, Samuele; Carina, Valeria; Bellavia, Daniele; Conigliaro, Alice; Alessandro, Riccardo; Fini, Milena; Conaldi, Pier Giulio; Giavaresi, Gianluca.

In: Carcinogenesis, 10.07.2019.

Research output: Contribution to journalArticle

Raimondi, Lavinia ; De Luca, Angela ; Gallo, Alessia ; Costa, Viviana ; Russelli, Giovanna ; Cuscino, Nicola ; Manno, Mauro ; Raccosta, Samuele ; Carina, Valeria ; Bellavia, Daniele ; Conigliaro, Alice ; Alessandro, Riccardo ; Fini, Milena ; Conaldi, Pier Giulio ; Giavaresi, Gianluca. / Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs. In: Carcinogenesis. 2019.
@article{9ae018957441489a819aa7e32bec71cc,
title = "Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs",
abstract = "Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodelling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the miRNA cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and Huvec cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment, also by a specific packaging of miRNAs.",
keywords = "exosomes, microRNAs profiling, osteosarcoma, tumor microenvironment",
author = "Lavinia Raimondi and {De Luca}, Angela and Alessia Gallo and Viviana Costa and Giovanna Russelli and Nicola Cuscino and Mauro Manno and Samuele Raccosta and Valeria Carina and Daniele Bellavia and Alice Conigliaro and Riccardo Alessandro and Milena Fini and Conaldi, {Pier Giulio} and Gianluca Giavaresi",
note = "{\circledC} The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",
year = "2019",
month = "7",
day = "10",
doi = "10.1093/carcin/bgz130",
language = "English",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs

AU - Raimondi, Lavinia

AU - De Luca, Angela

AU - Gallo, Alessia

AU - Costa, Viviana

AU - Russelli, Giovanna

AU - Cuscino, Nicola

AU - Manno, Mauro

AU - Raccosta, Samuele

AU - Carina, Valeria

AU - Bellavia, Daniele

AU - Conigliaro, Alice

AU - Alessandro, Riccardo

AU - Fini, Milena

AU - Conaldi, Pier Giulio

AU - Giavaresi, Gianluca

N1 - © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2019/7/10

Y1 - 2019/7/10

N2 - Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodelling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the miRNA cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and Huvec cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment, also by a specific packaging of miRNAs.

AB - Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodelling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the miRNA cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and Huvec cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment, also by a specific packaging of miRNAs.

KW - exosomes

KW - microRNAs profiling

KW - osteosarcoma

KW - tumor microenvironment

U2 - 10.1093/carcin/bgz130

DO - 10.1093/carcin/bgz130

M3 - Article

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

ER -