Expression of CXCL14 and its anticancer role in breast cancer
Expression of CXCL14 and its anticancer role in breast cancer
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CXCL14在乳腺癌中的表达及其抗癌作用
DOI：
10.1007/s10549-012-2206-2
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发表时间：
2012-10-01
影响因子：
3.8
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Gu, Xiao-Li;Ou, Zhou-Luo;Shao, Zhi-Ming
CXCL 14，也称为乳腺和肾脏表达的趋化因子，最初被鉴定为在肾脏和乳腺中高度表达的趋化因子。CXCL 14在人乳腺癌中的确切功能尚不清楚，但在头颈部鳞状细胞癌、肺癌、前列腺癌等多种肿瘤中已被证实具有抗肿瘤作用，本研究试图阐明CXCL 14与乳腺癌的关系.采用逆转录-PCR和western blot检测2株正常乳腺上皮细胞系和6株乳腺癌细胞系中CXCL 14的表达。采用稳定转染法建立CXCL 14高表达细胞株（MDA-MB-231 HM-CXCL 14），检测CXCL 14对MDA-MB-231 HM-CXCL 14体外增殖和侵袭能力的影响。我们用MDA-MB-231 HM-CXCL 14细胞建立了SCID小鼠的正交异性异种移植瘤模型，并探讨了CXCL 14过表达对体内肿瘤生长和转移的影响。同时采用免疫组化法检测208例乳腺癌组织中CXCL 14的表达水平，探讨CXCL 14与乳腺癌预后的关系。乳腺癌细胞系中CXCL 14 mRNA表达较低，MDA-MB-231 HM表达最低水平的CXCL 14 mRNA。CXCL 14的过表达在体外抑制细胞增殖和侵袭，在体内减弱异种移植瘤的生长和肺转移。CXCL 14蛋白水平与所有患者的总生存期以及有淋巴结转移的患者呈正相关，与淋巴结转移呈负相关。我们的研究首次表明，CXCL 14是乳腺癌生长和转移的负调节因子。该基因的重新表达或上调可能为将来乳腺癌的治疗提供新的策略。
CXCL14, also known as breast and kidney-expressed chemokine, was initially identified as a chemokine highly expressed in the kidney and breast. The exact function of CXCL14 in human breast cancer is still unclear, although it has been testified to play an anti-tumor role in other tumors, including head and neck squamous cell carcinoma, lung cancer, prostate cancer, and so on. In this study, we tried to demonstrate the relationship between CXCL14 and breast cancer. CXCL14 expressions were detected by reverse transcription-PCR and western blot in 2 normal breast epithelial cell lines and 6 breast cancer cell lines. The effects of CXCL14 on the proliferation and invasion in vitro were tested using the CXCL14-overexpressing cells (MDA-MB-231HM-CXCL14) which were established by stable transfection. We established an orthotropic xenograft tumor model in SCID mice using the MDA-MB-231HM-CXCL14 cells and explored the influence of CXCL14 overexpression on tumor growth and metastasis in vivo. Furthermore, we detected the protein level of CXCL14 in 208 breast cancer patients by immunohistochemistry and discussed the correlation between CXCL14 and the prognosis of breast cancer. CXCL14 mRNA expression is lower in breast cancer cell lines, and MDA-MB-231HM express the lowest levels of CXCL14 mRNA. Overexpression of CXCL14 inhibited cell proliferation and invasion in vitro and attenuated xenograft tumor growth and lung metastasis in vivo. CXCL14 protein level is positively correlated to the overall survival of all patients as well as the patients with lymph node metastasis, and it has a negative correlation with the lymph node metastasis. Our study showed for the first time that CXCL14 is a negative regulator of growth and metastasis in breast cancer. The re-expression or up-regulation of this gene may provide a novel strategy in breast cancer therapy in the future.