Cited by 266Bone Metabolism and DiseasesMicroRNA in disease regulationBone health and treatments

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Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis

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Ell, Brian, Mercatali, Laura, Ibrahim, Toni, Campbell, Neil, Schwarzenbach, Heidi, Pantel, Klaus, Amadori, Dino, Kang, Yibin·2013·Cancer Cell

DOI 10.1016/j.ccr.2013.09.008PMC PMC3832956

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Abstract

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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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
ORCID: Mercatali, Laura
Ibrahim, Toni
Schwarzenbach, Heidi
Pantel, Klaus
Kang, Yibin
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2013-10
Volume: 24
Issue: 4
Pages: 542-556
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2013.09.008
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
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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Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis

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