The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer
The role and clinical significance of the CXCL17-CXCR8 (GPR35) axis in breast cancer
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DOI：
10.1016/j.bbrc.2017.09.113
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发表时间：
2017-11-25
影响因子：
3.1
通讯作者：
Ou, Zhou Luo
中科院分区：
文献类型：
--
作者：
Guo, Ya Jie;Zhou, Yu Jie;Ou, Zhou Luo
背景：趋化因子配体17（CXCL 17）是趋化因子家族的最新成员。然而，它在各种癌症类型中的功能尚不清楚。G蛋白偶联受体35（GPR 35）被鉴定为CXCL 17的受体，最近被命名为CXCR 8。方法：采用Western blot和免疫组化方法检测CXCL 17和CXCR 8（GPR 35）在乳腺癌细胞系和组织微阵列（TMA）中的表达。结果：CXCL 17和CXCR 8（GPR 35）在乳腺癌细胞系中呈高表达，CXCL 17和CXCR 8（GPR 35）在乳腺癌细胞系中呈高表达。两者在乳腺癌组织中的表达均高于癌旁正常组织。尽管CXCL 17在体外乳腺癌细胞中可以与CXCR 8（GPR 35）相互作用，但未发现这两种标记物在乳腺癌组织中的表达相关性显著。CXCR 8（GPR 35）的表达与肿瘤的组织学分级和Ki-67的表达有关。尽管未发现CXCL 17与任何临床病理学特征具有统计学相关性，但发现其与较短的总生存期相关，并且是乳腺癌预后不良的独立标志物。此外，CXCL 17被发现可以促进乳腺癌细胞在体外和体内的增殖和迁移。结论：我们首次研究了CXCL 17-CXCR 8（GPR 35）轴在乳腺癌中的作用。CXCL 17是一个潜在的癌基因和有前途的治疗靶点，是乳腺癌患者预后不良的独立生物标志物，在体内外均能促进乳腺癌细胞的增殖和迁移。(C)2017爱思唯尔公司All rights reserved.
Background: Chemokine (C-X-C motif) ligand 17 (CXCL17) is the latest member of the chemokine family. However, its function in various cancer types is unknown. The G protein-coupled receptor 35 (GPR35) was identified as the receptor of CXCL17 and named recently as CXCR8. The function of the CXCL17CXCR8 (GPR35) biological axis in cancer has not been reported.Methods: The expression of CXCL17 and CXCR8 (GPR35) in breast cancer cell lines and a tissue micro array (TMA) was detected through western blot and immunohistochemistry (IHC). Expression data in IHC were analyzed using clinicopatholigical and survival information.Results: CXCL17 and CXCR8 (GPR35) were found to be variably expressed in breast cancer cell lines. Both expressed higher in breast cancer tissue than normal adjacent tissue. Although CXCL17 can interact with CXCR8 (GPR35) in breast cancer cells in vitro, the expression correlation between these two markers in breast cancer tissue was not found to be significant. As to clinical significance, CXCR8 (GPR35) expression was found to be significantly associated with advanced histological grade and higher proliferation rate indicated by Ki-67 expression. Although CXCL17 was not found to statistically correlate with any clinicopathological characteristics, it was found to be associated with shorter overall survival and is an independent marker of poor prognosis in breast cancer. In addition, CXCL17 was found to promote proliferation and migration of breast cancer cells in vitro and in vivo.Conclusions: We investigated the role of the CXCL17-CXCR8 (GPR35) axis in breast cancer for the first time. CXCL17 is a potential oncogene and promising therapeutic target, is an independent biomarker of poor prognosis in patients with breast cancer, and can promote proliferation and migration of breast cancer cells in vitro and in vivo. (C) 2017 Elsevier Inc. All rights reserved.