Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs
Academic Article
Publication Date:
2020
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 remodeling 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 micro RNA (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 hTert immortalized umbilical vein endothelial 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.
Iris type:
01.01 Articolo in rivista
Keywords:
alkaline phosphatase; calnexin; cathepsin K; CD81 antigen; interleukin 6; interleukin 8; messenger RNA; microRNA; microRNA 125a; microRNA 126; microRNA 128; microRNA 148a; microRNA 151a; microRNA 16; microRNA 182; microRNA 186; microRNA 1908; microRNA 193b; microRNA 21; microRNA 214; microRNA 23a; microRNA 301a; microRNA 331; microRNA 941; osteopontin; transcription factor RUNX2; unclassified drug; vasculotropin A; microRNA; tumor marker; animal cell; Article; biological phenomena and functions concerning the entire organism; bone remodeling; cancer growth; carcinogenesis; cell differentiation; computer model; confocal microscopy; controlled study; down regulation; endothelium cell; enzyme linked immunosorbent assay; exosome; gene expression; hierarchical clustering; human; human cell; in vitro study; MG-63 cell line; nonhuman; osteoclast; osteoclastogenesis; osteolysis; osteosarcoma cell; overall survival; photon correlation spectroscopy; polyacrylamide gel electrophoresis; priority journal; protein expression; real time polymerase chain reaction; RNA fingerprinting; RNA sequencing; SaOS-2 cell line; tumor microenvironment; U2OS cell line; umbilical vein endothelial cell; upregulation; Western blotting; bone tumor; cell culture; cell motion; cell proliferation; exosome; gene expression profiling; gene expression regulation; genetics; metabolism; neovascularization (pathology); osteosarcoma; pathology; tumor microenvironment; vascular endothelium; Biomarkers; Tumor; Bone Neoplasms; Cell Movement; Cell Proliferation; Cells; Cultured; Endothelium; Vascular; Exosomes; Gene Expression Profiling; Gene Expression Regulation; Neoplastic; Humans; MicroRNAs; Neovascularization; Pathologic; Osteosarcoma; Tumor Microenvironment
List of contributors:
Manno, Mauro; Raccosta, Samuele
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