Involvement of a Novel Chemokine Decoy Receptor CCX-CKR in Breast Cancer Growth, Metastasis and Patient Survival
Involvement of a Novel Chemokine Decoy Receptor CCX-CKR in Breast Cancer Growth, Metastasis and Patient Survival
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DOI：
10.1158/1078-0432.ccr-08-2495
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发表时间：
2009-05-01
影响因子：
11.5
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Feng, Lan-Yun;Ou, Zhou-Luo;Shao, Zhi-Ming
目的：趋化因子和趋化因子受体的生物学轴，如CXCR 4/CXCL 12、CCR 7/CCL 19（CCL 21）、CCR 9/CCL 25和CXCR 5/CXCL 13，参与癌症的生长和转移。本研究旨在探讨非典型趋化因子结合物CCX-CKR作为CCL 19、CCL 21、CCL 25和CXCL 13的清除剂在人乳腺癌中的潜在调节作用。实验设计：在细胞系、动物模型和临床样本中研究CCX-CKR在人乳腺癌中的作用。过表达CCX-CKR在体外抑制癌细胞增殖和侵袭，在体内减弱异种移植瘤生长和肺转移。CCX-CKR可由细胞因子如白细胞介素-1 β、肿瘤坏死因子-α和IFN-γ调节。CCX-CKR的缺乏或低表达与乳腺癌患者的低生存率相关。在人乳腺癌组织中观察到CCX-CKR与淋巴结转移显著相关。CCX-CKR状态是乳腺癌patient.Conclusion无病生存的一个独立的预后因素：我们首次发现，CCX-CKR是一个负调节乳腺癌的生长和转移，主要是通过隔离的稳态趋化因子和随后的抑制瘤内新生血管。这一发现可能会导致一种新的治疗乳腺癌的策略。
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.