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.

Raimondi, L., De Luca, A., Gallo, A., Costa, V., Russelli, G., Cuscino, N., et al. (2019). Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs. CARCINOGENESIS, 41(5), 666-677 [10.1093/carcin/bgz130].

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

Conigliaro, Alice;Alessandro, Riccardo;
2019-01-01

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.
Settore BIO/13 - Biologia Applicata
Raimondi, L., De Luca, A., Gallo, A., Costa, V., Russelli, G., Cuscino, N., et al. (2019). Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs. CARCINOGENESIS, 41(5), 666-677 [10.1093/carcin/bgz130].
File in questo prodotto:
File Dimensione Formato  
Raimondi et al 2019.pdf

Solo gestori archvio

Tipologia: Post-print
Dimensione 958.17 kB
Formato Adobe PDF
958.17 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
bgz130.pdf

Solo gestori archvio

Tipologia: Versione Editoriale
Dimensione 9.35 MB
Formato Adobe PDF
9.35 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/370557
Citazioni
  • ???jsp.display-item.citation.pmc??? 51
  • Scopus 54
  • ???jsp.display-item.citation.isi??? 60
social impact