CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro

• DOI: 10.3892/or.17.6.1511
• Publication Date: 2014-03-10T03:50:27Z
• Authors: Keiichi Koizumi; Yoko Kozawa; Yasukata Ohashi; Eliane Nakamura; Yasushi Aozuka; Hiroaki Sakurai; Katsuyuki Ichiki; Yoshinori Doki; Takuro Misaki; Ikuo Saiki
• Keywords: Receptors, CCR7; Lung Neoplasms; Chemokine CCL21; Chemotaxis; Vascular Cell Adhesion Molecule-1; Mice, Inbred Strains; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Cell Movement; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chemokines, CC; Lymphatic Metastasis; Cell Adhesion; Animals; Humans; Receptors, Chemokine; Lymph Nodes; Neoplasm Transplantation

To develop new therapy strategies for lung cancer, we established an animal model, which reflects the clinical features of mediastinal lymph node metastasis of lung cancer. This study was designed to determine whether CCL21 induced biological functions associated with the metastasis of highly lymph node metastatic human non-small cell lung cancer (NSCLC) selected by our model. Orthotopic intrapulmonary implantation of human NSCLC (Lu-99 and A549) was performed to analyze the metastatic characteristics of these cells. The expression of CCR7, which is a receptor of CCL21, was detected using CCL19 [also called EBI1-ligand chemokine (ELC)]-Fc chimera by flow cytometric analysis. The effects of CCL21 on the migration, adhesion and growth of human NSCLC were investigated. After orthotopic implantation of human NSCLC cell lines, Lu-99, but not A549, metastasized to mediastinal lymph nodes, forming large size nodules, and expressed CCR7 on the surface. Accordingly, its ligand CCL21 induced chemotactic migration and alpha4beta1-mediated adhesion to VCAM-1 of Lu-99. The expression of CCR7 and vigorous responses to its ligand CCL21 potentially account for lymph node metastasis of a human NSCLC line Lu-99.