Doki Y, Murakami K, Yamaura T, Sugiyama S, Misaki T, Saiki I
Department of Pathogenic Biochemistry, Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Br J Cancer. 1999 Mar;79(7-8):1121-6. doi: 10.1038/sj.bjc.6690178.
This study is designed to establish a pulmonary tumour model to investigate the biology and therapy of lung cancer in mice. Current methods for forming a solitary intrapulmonary nodule and subsequent metastasis to mediastinal lymph nodes are not well defined. Lewis lung carcinoma (LLC) cell suspensions were orthotopically introduced into the lung parenchyma of C57/BL6 mice via a limited skin incision without thoracotomy followed by direct puncture through the intercostal space. The implantation process was performed within approximately 50 s per mouse, and the operative mortality was less than 5%. Single pulmonary nodules developed at the implanted site in 93% of animals and subsequent mediastinal lymph node metastasis was observed in all mice that formed a lung nodule after intrapulmonary implantation. The size of tumour nodule and the weight of mediastinal lymph node increased in a time-dependent manner. The mean survival time of mice implanted successfully with LLC cells was 21+/-2 days (range 19-24 days). Histopathological analysis revealed that no metastatic tumour was detectable in the mediastinal lymph nodes on day 11, but metastatic foci at mediastinal lymph nodes were clearly observed on days 17 and 21 after implantation. Other metastases in distant organs or lymph nodes were not observed at 21 days after the implantation. Comparative studies with intrapleural and intravenous injections of LLC cells suggest that the mediastinal lymph node metastasis by intrapulmonary implantation is due to the release of tumour cells from the primary nodule, and not due to extrapulmonary leakage of cells. An intravenous administration of cis-diamine dichloro platinum on day 1 after tumour implantation tended to suppress the primary tumour nodule and significantly inhibited lymph node metastasis. Thus, a solitary pulmonary tumour nodule model with lymph node metastasis approximates clinical lung cancer and may provide a useful basis for lung cancer research.
本研究旨在建立一种肺肿瘤模型，以研究小鼠肺癌的生物学特性和治疗方法。目前形成孤立性肺内结节并随后转移至纵隔淋巴结的方法尚不明确。通过有限的皮肤切口，在不进行开胸手术的情况下，经肋间间隙直接穿刺，将Lewis肺癌（LLC）细胞悬液原位导入C57/BL6小鼠的肺实质。每只小鼠的植入过程约在50秒内完成，手术死亡率低于5%。93%的动物在植入部位形成单个肺结节，所有肺内植入后形成肺结节的小鼠均观察到随后的纵隔淋巴结转移。肿瘤结节大小和纵隔淋巴结重量呈时间依赖性增加。成功植入LLC细胞的小鼠平均生存时间为21±2天（范围19 - 24天）。组织病理学分析显示，植入后第11天纵隔淋巴结未检测到转移性肿瘤，但在植入后第17天和第21天纵隔淋巴结明显观察到转移灶。植入后21天未观察到远处器官或淋巴结的其他转移。与胸膜内和静脉注射LLC细胞的对比研究表明，肺内植入导致的纵隔淋巴结转移是由于原发结节释放肿瘤细胞，而非细胞的肺外渗漏。肿瘤植入后第1天静脉注射顺二氯二氨铂倾向于抑制原发肿瘤结节，并显著抑制淋巴结转移。因此，具有淋巴结转移的孤立性肺肿瘤结节模型近似临床肺癌，可为肺癌研究提供有用的基础。
