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人肺腺癌支气管内原位播散——致瘤性、侵袭和转移的特征

Intrabronchial orthotopic propagation of human lung adenocarcinoma--characterizations of tumorigenicity, invasion and metastasis.

作者信息

Mase Kentaro, Iijima Tatsuo, Nakamura Naoko, Takeuchi Tomoyo, Onizuka Masataka, Mitsui Toshio, Noguchi Masayuki

机构信息

Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 3058575, Japan.

出版信息

Lung Cancer. 2002 Jun;36(3):271-6. doi: 10.1016/s0169-5002(02)00004-1.

DOI:10.1016/s0169-5002(02)00004-1
PMID:12009237
Abstract

Using the intrabronchial orthotopic propagation method, we evaluated the biological characteristics of human adenocarcinoma cell lines in vivo and examined the expressions of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) and their related proteins. Nine human lung adenocarcinoma cell lines, including A549, NCI-H23, NCI-H322, NCI-H358, Calu-3, PC-14, LC-2/ad, RERF-LC-KJ and PL16T, were injected into the peripheral bronchi of mice using this method. The mice were sacrificed at 4 and 8 weeks after tumor cell propagation and the lungs and other organs were observed macroscopically and histologically. We classified the adenocarcinoma cell lines, according to their intrapulmonary tumorigenicity, into the following three groups: (A) those that showed a high incidence of intrapulmonary implantation (>50%) (A549 and NCI-H358). A549 showed mediastinal lymph node metastasis and pleural dissemination; (B) those that showed a low incidence of intrapulmonary implantation (PC-14, NCI-H322, NCI-H23, Calu-3, and LC-2/ad); (C) those that showed no tumorigenicity in the lung (RERF-LC-KJ and PL16T). In order to characterize the biological differences between each cell line, we investigated the expressions of MMP-2 and MMP-9 and their related molecules by northern blot analysis. The expressions of MMP-2 and MMP-9 and their activators (membrane-type 1-MMP and urokinase-type plasminogen activator) were thought to be associated with the growth, invasion and metastasis of the human lung adenocarcinoma cell lines examined.

摘要

采用支气管内原位接种法,我们在体内评估了人腺癌细胞系的生物学特性,并检测了基质金属蛋白酶-2(MMP-2)和-9(MMP-9)及其相关蛋白的表达。使用该方法将包括A549、NCI-H23、NCI-H322、NCI-H358、Calu-3、PC-14、LC-2/ad、RERF-LC-KJ和PL16T在内的9种人肺腺癌细胞系注入小鼠外周支气管。在肿瘤细胞接种后4周和8周处死小鼠,对肺和其他器官进行大体和组织学观察。根据肺内致瘤性,我们将腺癌细胞系分为以下三组:(A)肺内种植发生率高(>50%)的细胞系(A549和NCI-H358)。A549出现纵隔淋巴结转移和胸膜播散;(B)肺内种植发生率低的细胞系(PC-14、NCI-H322、NCI-H23、Calu-3和LC-2/ad);(C)在肺内无致瘤性的细胞系(RERF-LC-KJ和PL16T)。为了表征各细胞系之间的生物学差异,我们通过Northern印迹分析研究了MMP-2和MMP-9及其相关分子的表达。MMP-2和MMP-9及其激活剂(膜型1-MMP和尿激酶型纤溶酶原激活剂)的表达被认为与所检测的人肺腺癌细胞系的生长、侵袭和转移有关。

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