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Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis

Authors
 Sun Kyoung Lee  ;  Kwang-Kyun Park  ;  Hyun-Jeong Kim  ;  Junhee Park  ;  Seung Hwa Son  ;  Ki Rim Kim  ;  Won-Yoon Chung 
Citation
 Scientific Reports, Vol.7(1) : 9610, 2017 
Journal Title
 Scientific Reports 
Issue Date
2017
Abstract
Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expression in breast cancer subtypes, particularly the basal-like subtype. Metastasis-free survival and overall survival were decreased in the breast cancer patients with high CCL20 expression. We further confirmed the role of CCL20 in breast cancer bone metastasis. Intraperitoneal administration of anti-CCL20 antibodies inhibited osteolytic breast cancer bone metastasis in mice. Treatment with CCL20 noticeably promoted cell invasion and the secretion of MMP-2/9 in the basal-like triple-negative breast cancer cell lines, not the luminal. Moreover, CCL20 elevated the receptor activator of nuclear factors kappa-B ligand/osteoprotegerin ratio in breast cancer and osteoblastic cells and mediated the crosstalk between these cells. Collectively, HuR-regulated CCL20 may be an attractive therapeutic target for breast cancer bone metastasis.
Files in This Item:
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DOI
10.1038/s41598-017-09040-4
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
김현정(Kim, Hyun-Jeong) ORCID logo https://orcid.org/0000-0003-4608-2120
박광균(Park, Kwang Kyun)
박준희(Park, Jun Hee)
이선경(Lee, Sun Kyoung) ORCID logo https://orcid.org/0000-0002-3707-8050
정원윤(Chung, Won Yoon) ORCID logo https://orcid.org/0000-0001-8428-9005
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160655
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