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

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

Risultato della ricerca: Articlepeer review

22 Citazioni (Scopus)


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.
Lingua originaleEnglish
pagine (da-a)666-677
Numero di pagine12
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

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