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Expression of CXCL14 and its anticancer role in breast cancer

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Abstract

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.

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Acknowledgments

This research was supported in part by the grants from the National Basic Research Program of China (2006CB910501), National Natural Science Foundation of China (30570695, 81172506). We would like to thank Dr. Takahiko Hara who works for the Tokyo Metropolitan Institute of Medical Science, Japan for kindly providing the CXCL14 gene fragment.

Conflict of interest

The authors have declared that no conflict of interests exists.

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Authors and Affiliations

  1. Department of Oncology, Cancer Hospital, Breast Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China

    Xiao-Li Gu, Zhou-Luo Ou, Feng-Juan Lin, Xiao-Li Yang, Jian-Min Luo, Zhen-Zhou Shen & Zhi-Ming Shao

  2. Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Fudan University, 270 Dong An Road, Shanghai, 200032, People’s Republic of China

    Zhi-Ming Shao

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  1. Xiao-Li Gu
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  2. Zhou-Luo Ou
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Correspondence to Zhi-Ming Shao.

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Xiao-Li Gu and Zhou-Luo Ou contributed equally to the work.

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Gu, XL., Ou, ZL., Lin, FJ. et al. Expression of CXCL14 and its anticancer role in breast cancer. Breast Cancer Res Treat 135, 725–735 (2012). https://doi.org/10.1007/s10549-012-2206-2

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  • DOI: https://doi.org/10.1007/s10549-012-2206-2

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