TY - JOUR
T1 - Tumor-Induced Osteoclast miRNA Changes as Regulators and Biomarkers of Osteolytic Bone Metastasis
AU - Ell, Brian
AU - Mercatali, Laura
AU - Ibrahim, Toni
AU - Campbell, Neil
AU - Schwarzenbach, Heidi
AU - Pantel, Klaus
AU - Amadori, Dino
AU - Kang, Yibin
N1 - Funding Information:
We thank C. DeCoste for assistance with flow cytometry and E. Williams, F. Miller, and R.L. Anderson for the TSU-PR1, 4T1 cell lines series. This research was supported by grants from the Komen for the Cure (KG110464), the Department of Defense (BC123187), the Brewster Foundation, the National Institutes of Health (R01CA134519 and R01CA141062), and the Champalimaud Foundation to Y.K. and the European Research Council (Advanced Investigator Grant “DISSECT,” 269081), Deutsche Forschungsgemeinschaft, and German Minister of Education and Research (BMBF) to K.P. This research was also supported by the Preclinical Imaging and Flow Cytometry Shared Resources of the Cancer Institute of New Jersey (P30CA072720).
PY - 2013/10/14
Y1 - 2013/10/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84885368280&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885368280&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2013.09.008
DO - 10.1016/j.ccr.2013.09.008
M3 - Article
C2 - 24135284
AN - SCOPUS:84885368280
SN - 1535-6108
VL - 24
SP - 542
EP - 556
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -