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CCL21/CCR7 axis activating chemotaxis accompanied with epithelial–mesenchymal transition in human breast carcinoma

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Abstract

Secondary lymphoid tissue chemokine (SLC/CCL21) and its receptor CCR7 have been implicated in lymph node metastasis, whereas the mechanism of which remains unclear. Epithelial–mesenchymal transition (EMT) plays an important role in invasion and migration of cancer cells. We presumed that CCL21/CCR7 axis activates EMT process to induce cancer cell invasion and metastasis. Firstly, the expressions of CCR7 and EMT markers were examined by immunohistochemical staining in the primary breast carcinoma tissues from 60 patients who underwent radical mastectomy. Then, we investigated whether CCL21/CCR7 induces EMT process during mediating cancer cell invasion or migration in vitro. By immunohistolochemistry, high expressions of CCR7, Slug and N-cadherin were seen in 60, 65, and 76.67 % of tumors, respectively, and significantly associated with lymph node metastases as well as clinical pathological stage. Furthermore, the CCR7 expression was significantly correlated to Slug and N-cadherin. In vitro, stimulating breast cancer cell lines 1428, MCF-7 and MDA-MB-231 with CCL21, the invasion and migration of tumor cells were promoted, and simultaneously, EMT phenotype of tumor cells was enhanced, including down-regulation of E-cadherin, up-regulation of Slug, Vimentin and N-cadherin at both protein and mRNA levels. Inversely, knockdown of CCR7 by shRNA suppressed tumor cell invasion, migration and EMT phenotype induced by CCL21. These results indicated that CCL21/CCR7 axis could activate EMT process during chemotaxis of breast carcinoma cells.

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Acknowledgments

This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2013HM096), and the Medicine and health care in Shandong province science and technology development plan Project (No. 2013WS0207). We greatly thank the members of the Tian Hua laboratory for their insightful discussions and advice on this Project.

Conflict of interest

Authors state that there are no conflicts of interest to disclose.

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Authors and Affiliations

  1. Human Anatomy Department, Medicine School of Shandong University, 44#, Wenhua Xi Road, Jinan, 250012, Shandong, China

    Fei Li, Ning Suo, Zongpu Zhang, Fangzhu Wan, Guangxin Zhong, Yan Qu, Kwanele Siphelele Ntaka & Hua Tian

  2. Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Zhigeng Zou

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  1. Fei Li
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  2. Zhigeng Zou
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Correspondence to Hua Tian.

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Li, F., Zou, Z., Suo, N. et al. CCL21/CCR7 axis activating chemotaxis accompanied with epithelial–mesenchymal transition in human breast carcinoma. Med Oncol 31, 180 (2014). https://doi.org/10.1007/s12032-014-0180-8

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  • DOI: https://doi.org/10.1007/s12032-014-0180-8

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