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
Pages (from-to)1-12
Number of pages12
JournalCarcinogenesis
Volume2019
DOIs
Publication statusPublished - 2020

Keywords

  • exosomes
  • microRNAs profiling
  • osteosarcoma
  • tumor microenvironment

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