CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro.
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.
Koizumi
Keiichi
K
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan. kkoizumi@inm.u-toyama.ac.jp
Kozawa
Yoko
Y
Ohashi
Yasukata
Y
Nakamura
Eliane Shizuka
ES
Aozuka
Yasushi
Y
Sakurai
Hiroaki
H
Ichiki
Katsuyuki
K
Doki
Yoshinori
Y
Misaki
Takuro
T
Saiki
Ikuo
I
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis; D004195:Disease Models, Animal; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019010:Vascular Cell Adhesion Molecule-1