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CCL28-induced RARβ expression inhibits oral squamous cell carcinoma bone invasion

Authors
 Junhee Park  ;  Xianglan Zhang  ;  Sun Kyoung Lee  ;  Na-Young Song  ;  Seung Hwa Son  ;  Ki Rim Kim  ;  Jae Hoon Shim  ;  Kwang-Kyun Park  ;  Won-Yoon Chung 
Citation
 JOURNAL OF CLINICAL INVESTIGATION, Vol.129(12) : 5381-5399, 2019 
Journal Title
 JOURNAL OF CLINICAL INVESTIGATION 
ISSN
 0021-9738 
Issue Date
2019
Keywords
Bone disease ; Cancer ; Chemokines ; Oncology
Abstract
Oral squamous cell carcinoma (OSCC) frequently invades the maxillary or mandibular bone, and this bone invasion is closely associated with poor prognosis and survival. Here, we show that CCL28 functions as a negative regulator of OSCC bone invasion. CCL28 inhibited invasion and epithelial-mesenchymal transition (EMT), and its inhibition of EMT was characterized by induced E-cadherin expression and reduced nuclear localization of β-catenin in OSCC cells with detectable RUNX3 expression levels. CCL28 signaling via CCR10 increased retinoic acid receptor-β (RARβ) expression by reducing the interaction between RARα and HDAC1. In addition, CCL28 reduced RANKL production in OSCC and osteoblastic cells and blocked RANKL-induced osteoclastogenesis in osteoclast precursors. Intraperitoneally administered CCL28 inhibited tumor growth and osteolysis in mouse calvaria and tibia inoculated with OSCC cells. RARβ expression was also increased in tumor tissues. In patients with OSCC, low CCL28, CCR10, and RARβ expression levels were highly correlated with bone invasion. Patients with OSCC who had higher expression of CCL28, CCR10, or RARβ had significantly better overall survival. These findings suggest that CCL28, CCR10, and RARβ are useful markers for the prediction and treatment of OSCC bone invasion. Furthermore, CCL28 upregulation in OSCC cells or CCL28 treatment can be a therapeutic strategy for OSCC bone invasion.
Full Text
https://www.jci.org/articles/view/125336
DOI
10.1172/JCI125336
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
Yonsei Authors
Park, Kwang Kyun(박광균)
Park, Jun Hee(박준희)
Son, Seung Hwa(손승화)
Song, Na-Young(송나영) ORCID logo https://orcid.org/0000-0001-8658-7049
Lee, Sun Kyoung(이선경) ORCID logo https://orcid.org/0000-0002-3707-8050
Zhang, Xiang Lan(장향란)
Chung, Won Yoon(정원윤) ORCID logo https://orcid.org/0000-0001-8428-9005
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174670
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