International journal of molecular sciences, 2022-01, Vol.23 (3), p.1285
2022
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- Autor(en) / Beteiligte
- Titel
- Exosomal miRNAs from Prostate Cancer Impair Osteoblast Function in Mice
- Ist Teil von
- International journal of molecular sciences, 2022-01, Vol.23 (3), p.1285
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2022
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms23031285Titel-ID: cdi_doaj_primary_oai_doaj_org_article_b19335e18b3d459a978e9ec07f1e5bb5
- Format
- –
- Schlagworte
- Androgens, Animals, Biomedical materials, Bone and Bones - metabolism, Bone and Bones - physiology, Bone cancer, Bone lesions, bone metastases, Bone morphogenetic protein 2, Bone remodeling, Cell Communication, Cell Line, Tumor, Cell Proliferation, Crosstalk, Exosome Multienzyme Ribonuclease Complex - genetics, Exosome Multienzyme Ribonuclease Complex - metabolism, Exosomes - genetics, Extracellular vesicles, Extracellular Vesicles - metabolism, Gene expression, Gene Expression - genetics, Gene Expression Profiling - methods, Gene Expression Regulation, Neoplastic - genetics, Glial stem cells, Inflammation, Lesions, Male, Malignancy, Membranes, Mesenchymal Stem Cells, Metastases, Metastasis, Mice, Mice, Inbred C57BL, Microenvironments, MicroRNAs, MicroRNAs - genetics, Microscopy, miRNA, Nanoparticles, Ossification, Osteoblasts, Osteoblasts - physiology, Osteogenesis, Osteoprogenitor cells, osteoprogenitors, Prostate cancer, Prostatic Neoplasms - genetics, Proteins, Transcriptome - genetics, Transcriptomics, Tumor Microenvironment