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Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis
Open accessAbstract
Understanding the mechanism by which tumor cells influence osteoclast differentiation is crucial for improving treatment of osteolytic metastasis. Here, we report broad microRNA (miRNA) expression changes in differentiating osteoclasts after exposure to tumor-conditioned media, in part through activation of NFκB signaling by soluble intracellular adhesion molecule (sICAM1) secreted from bone-metastatic cancer cells. Ectopic expression of multiple miRNAs downregulated during osteoclastogenesis suppresses osteoclast differentiation by targeting important osteoclast genes. Intravenous delivery of these miRNAs in vivo inhibits osteoclast activity and reduces osteolytic bone metastasis. Importantly, serum levels of sICAM1 and two osteoclast miRNAs, miR-16 and miR-378, which are elevated in osteoclast differentiation, correlate with bone metastasis burden. These findings establish miRNAs as potential therapeutic targets and clinical biomarkers of bone metastasis.
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“Furthermore, exosome transport solves the problem of easy degradation of miRNAs in vivo, implying a new tumor therapy [50].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [50]
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Metadata
- Authors
- Ell, B., Mercatali, L., Ibrahim, T., Campbell, N., Schwarzenbach, H., Pantel, K., Amadori, D., & Kang, Y.
- Affiliations
- Princeton University (US)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Rutgers Cancer Institute (US)
- Universität Hamburg (DE)
- Corresponding author
- Kang, Yibin
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 24
- Issue
- 4
- Pages
- 542-556
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3832956
- OpenAlex
- W2054148405
- Cited by
- 266
- References
- 41
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 15 · 2021: 27 · 2020: 25 · 2019: 23 · 2018: 31 · 2017: 22 · 2016: 30 · 2015: 31 · 2014: 33 · 2013: 2
- FWCI
- 14.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA141062, R01CA134519, P30CA072720)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- osteoclastogenesis, osteolytic bone metastasis, microRNA, tumor-conditioned medium, NF-κB signaling, miR-16, miR-378, serum biomarkers, microRNA delivery, therapeutic target
- MeSH terms
- Animals, Bone Neoplasms, Bone Resorption, Humans, Neoplasm Metastasis, Osteoclasts, Osteolysis, Biomarkers, Tumor, NF-kappa B, Culture Media, Conditioned, Intercellular Adhesion Molecule-1, CD18 Antigens, MicroRNAs, Cell Line, Tumor, Mice
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