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Exosomal miRNAs from Prostate Cancer Impair Osteoblast Function in Mice
- 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.
- Subjects :
- Male
Osteoprogenitors
QH301-705.5
Gene Expression
Cell Communication
Exosomes
Catalysis
Bone and Bones
bone metastases
prostate cancer
osteoprogenitors
extracellular vesicles
miRNA
Inorganic Chemistry
Extracellular Vesicles
Mice
Osteogenesis
Cell Line, Tumor
Tumor Microenvironment
Animals
Physical and Theoretical Chemistry
Biology (General)
Molecular Biology
QD1-999
Spectroscopy
Cell Proliferation
Prostate cancer
Osteoblasts
Exosome Multienzyme Ribonuclease Complex
Bone metastases
Gene Expression Profiling
Organic Chemistry
Prostatic Neoplasms
Mesenchymal Stem Cells
General Medicine
Computer Science Applications
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Chemistry
MicroRNAs
Transcriptome
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....4be5d024bfe52326421a7e827de39c85