Koizumi Keiichi, Kozawa Yoko, Ohashi Yasukata, Nakamura Eliane Shizuka, Aozuka Yasushi, Sakurai Hiroaki, Ichiki Katsuyuki, Doki Yoshinori, Misaki Takuro, Saiki Ikuo
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
Oncol Rep. 2007 Jun;17(6):1511-6.
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.
为了开发肺癌的新治疗策略，我们建立了一种动物模型，该模型反映了肺癌纵隔淋巴结转移的临床特征。本研究旨在确定CCL21是否诱导了与我们模型所选择的高淋巴结转移性人非小细胞肺癌（NSCLC）转移相关的生物学功能。通过人NSCLC（Lu-99和A549）原位肺内植入来分析这些细胞的转移特征。使用CCL19 [也称为EBI1配体趋化因子（ELC）]-Fc嵌合体通过流式细胞术分析检测CCL21的受体CCR7的表达。研究了CCL21对人NSCLC迁移、黏附和生长的影响。人NSCLC细胞系原位植入后，Lu-99而非A549转移至纵隔淋巴结，形成大尺寸结节，并在表面表达CCR7。因此，其配体CCL21诱导了Lu-99的趋化迁移和α4β1介导的对VCAM-1的黏附。CCR7的表达及其对配体CCL21的强烈反应可能是人NSCLC细胞系Lu-99淋巴结转移的原因。
