Involvement of a Novel Chemokine Decoy Receptor CCX-CKR in Breast Cancer Growth, Metastasis and Patient Survival

被引：74
作者：
Feng, Lan-Yun [1 ]
Ou, Zhou-Luo [1 ]
Wu, Feng-Ying [1 ]
Shen, Zhen-Zhou [1 ]
Shao, Zhi-Ming [1 ]
机构：
[1] Fudan Univ, Breast Canc Inst, Canc Hosp, Dept Oncol,Shanghai Med Coll,Inst Biomed Sci, Shanghai 200032, Peoples R China
来源：
CLINICAL CANCER RESEARCH | 2009年 / 15卷 / 09期
基金：
中国国家自然科学基金;
关键词：
LYMPH-NODE METASTASIS; LUNG-CANCER; IN-VITRO; CELLS; EXPRESSION; CXCL13; CXCR5; CCR7; SEQUESTRATION; ACTIVATION;
D O I：
10.1158/1078-0432.CCR-08-2495
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Purpose: The biological axes of chemokines and chemokine receptors, such as CXCR4/CXCL12, CCR7/CCL19 (CCL21), CCR9/CCL25, and CXCR5/CXCL13, are involved in cancer growth and metastasis. This study is aimed at the potential regulatory role of atypical chemokine binder CCX-CKR, as a scavenger of CCL19, CCL21, CCL25, and CXCL13, in human breast cancer. Experimental Design: The role of CCX-CKR in human breast cancer was investigated in cell lines, animal models, and clinical samples. Results: Overexpression of CCX-CKR inhibited cancer cell proliferation and invasion in vitro and attenuated xenograft tumor growth and lung metastasis in vivo. CCX-CKR can be regulated by cytokines such as interleukin-1 beta tumor necrosis factor-alpha, and IFN-gamma. Lack or low expression of CCX-CKR correlated with a poor survival rate in the breast cancer patients. A significant correlation between CCX-CKR and lymph node metastasis was observed in human breast cancer tissues. CCX-CKR status was an independent prognostic factor for disease-free survival in breast cancer patients. Conclusion: We showed for the first time that CCX-CKR is a negative regulator of growth and metastasis in breast cancer mainly by sequestration of homeostatic chemokines and subsequent inhibition of intratumoral neovascularity. This finding may lead to a new therapeutic strategy against breast cancer.
引用
收藏
页码：2962 / 2970
页数：9
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