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

被引：295

作者：

Ell, Brian ^{[1
]}

Mercatali, Laura ^{[2
,3
]}

Ibrahim, Toni ^{[2
]}

Campbell, Neil ^{[4
]}

Schwarzenbach, Heidi ^{[5
]}

Pantel, Klaus ^{[5
]}

Amadori, Dino ^{[2
]}

Kang, Yibin ^{[1
,6
]}

机构：

[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

[2] IRCCS Sci Inst Romagna Study & Treatment Canc IRS, Osteoncol & Rare Tumors Ctr, I-47014 Meldola, Italy

[3] IRCCS Sci Inst Romagna Study & Treatment Canc IRS, Biosci Lab, I-47014 Meldola, Italy

[4] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA

[5] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Dept Tumor Biol, D-20246 Hamburg, Germany

[6] Rutgers Canc Inst New Jersey, Genom Instabil & Tumor Progress Program, New Brunswick, NJ 08903 USA

来源：

CANCER CELL | 2013年 / 24卷 / 04期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

BREAST-CANCER METASTASIS; MICRORNAS; MITF; DIFFERENTIATION; INVOLVEMENT; MODEL; TFE3;

D O I：

10.1016/j.ccr.2013.09.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 NF kappa B 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.

引用

页码：542 / 556

页数：15

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