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

Med Oncol. 2014 Sep;31(9):180. doi: 10.1007/s12032-014-0180-8. Epub 2014 Aug 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast / chemistry
  • Breast / metabolism
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Chemokine CCL21 / analysis
  • Chemokine CCL21 / metabolism*
  • Chemotaxis / physiology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Middle Aged
  • Receptors, CCR7 / analysis
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*


  • Biomarkers, Tumor
  • CCL21 protein, human
  • CCR7 protein, human
  • Chemokine CCL21
  • Receptors, CCR7