Back to Search Start Over

Exosomal miRNAs from Prostate Cancer Impair Osteoblast Function in Mice

Authors :
Giulia Furesi
Antonio Miguel de Jesus Domingues
Dimitra Alexopoulou
Andreas Dahl
Matthias Hackl
Johannes R. Schmidt
Stefan Kalkhof
Thomas Kurth
Hanna Taipaleenmäki
Stefanie Conrad
Christine Hofbauer
Martina Rauner
Lorenz C. Hofbauer
Publica
Source :
International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1285, International Journal of Molecular Sciences, Vol 23, Iss 1285, p 1285 (2022)
Publication Year :
2021

Abstract

Prostate cancer (PCa) is the most frequent malignancy in older men with a high propensity for bone metastases. Characteristically, PCa causes osteosclerotic lesions as a result of disrupted bone remodeling. Extracellular vesicles (EVs) participate in PCa progression by conditioning the pre-metastatic niche. However, how EVs mediate the cross-talk between PCa cells and osteoprogenitors in the bone microenvironment remains poorly understood. We found that EVs derived from murine PCa cell line RM1-BM increased metabolic activity, vitality, and cell proliferation of osteoblast precursors by >60%, while significantly impairing mineral deposition (−37%). The latter was further confirmed in two complementary in vivo models of ossification. Accordingly, gene and protein set enrichments of osteoprogenitors exposed to EVs displayed significant downregulation of osteogenic markers and upregulation of proinflammatory factors. Additionally, transcriptomic profiling of PCa-EVs revealed the abundance of three microRNAs, miR-26a-5p, miR-27a-3p, and miR-30e-5p involved in the suppression of BMP-2-induced osteogenesis in vivo, suggesting the critical role of these EV-derived miRNAs in PCa-mediated suppression of osteoblast activity. Taken together, our results indicate the importance of EV cargo in cancer-bone cross-talk in vitro and in vivo and suggest that exosomal miRNAs may contribute to the onset of osteosclerotic bone lesions in PCa.

Details

ISSN :
14220067
Volume :
23
Issue :
3
Database :
OpenAIRE
Journal :
International journal of molecular sciences
Accession number :
edsair.doi.dedup.....4be5d024bfe52326421a7e827de39c85