Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis
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Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. / Ell, Brian; Mercatali, Laura; Ibrahim, Toni; Campbell, Neil; Schwarzenbach, Heidi; Pantel, Klaus; Amadori, Dino; Kang, Yibin.
In: CANCER CELL, Vol. 24, No. 4, 14.10.2013, p. 542-56.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 - Copyright © 2013 Elsevier Inc. All rights reserved.
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 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.
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 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.
KW - Animals
KW - Antigens, CD18
KW - Bone Neoplasms
KW - Bone Resorption
KW - Cell Line, Tumor
KW - Culture Media, Conditioned
KW - Humans
KW - Intercellular Adhesion Molecule-1
KW - Mice
KW - MicroRNAs
KW - NF-kappa B
KW - Neoplasm Metastasis
KW - Osteoclasts
KW - Osteolysis
KW - Tumor Markers, Biological
U2 - 10.1016/j.ccr.2013.09.008
DO - 10.1016/j.ccr.2013.09.008
M3 - SCORING: Journal article
C2 - 24135284
VL - 24
SP - 542
EP - 556
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 4
ER -