CD164 regulates the tumorigenesis of ovarian surface epithelial cells through the SDF-1α/CXCR4 axis

Molecular Cancer

Research

Chu-Lien Kao¹  Hung-Cheng Lai²  Min-Wei Chen³  Ai-Fang Huang⁴  Shih-Ming Huang⁵  James Yi-Hsin Chan⁶ 

[1] Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Departments of Oncology and Pathology, National Taiwan University Hospital, Taipei 100, Taiwan, Republic of China;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, Republic of China;

关键词: Ovarian cancer;    CD164;    CXCR4;    SDF-1α;    Tumorigenesis;   

DOI  :  10.1186/1476-4598-12-115

 received in 2013-08-07, accepted in 2013-10-02,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundCD164 (endolyn), a sialomucin, has been reported to play a role in the proliferation, adhesion, and differentiation of hematopoietic stem cells. The potential association of CD164 with tumorigenicity remains unclear.MethodsThe clinicopathological correlation of ovarian cancer with CD164 was assessed in a 97-patient tumor tissue microarray. Overexpression or silence CD164 was to analyze the effect of CD164 on the proliferation, colony formation and apoptosis via a mouse xenograft and western blotting analysis. The subcellular localization of CD164 was collected in the immunohistochemical and confocal analysis.ResultsOur data demonstrated that higher expression levels of CD164 were identified in malignant ovarian cancer cell lines, such as SKOV3 and HeyA8. The clinicopathological correlation analysis showed that the upregulation of CD164 protein was significantly associated with tumor grade and metastasis. The overexpression of CD164 in human ovarian epithelial surface cells promoted cellular proliferation and colony formation and suppressed apoptosis. These tumorigenicity effects of CD164 were reconfirmed in a mouse xenograft model. We also found that the overexpression of CD164 proteins increased the amounts of CXCR4 and SDF-1α and activated the SDF-1α/CXCR4 axis, inducing colony and sphere formation. Finally, we identified the subcellular localization of CD164 in the nucleus and cytosol and found that nuclear CD164 might be involved in the regulation of the activity of the CXCR4 promoter.ConclusionsOur findings suggest that the increased expression of CD164 is involved in ovarian cancer progression via the SDF-1α/CXCR4 axis, which promotes tumorigenicity. Thus, targeting CD164 may serve as a potential ovarian cancer biomarker, and targeting CD164 may serve as a therapeutic modality in the management of high-grade ovarian tumors.

【 授权许可】

Unknown   
© Huang et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.