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

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

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

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 invivo 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.

Original languageEnglish (US)
Pages (from-to)542-556
Number of pages15
JournalCancer Cell
Volume24
Issue number4
DOIs
StatePublished - Oct 14 2013

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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