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Development of an experimental model for human tracheobronchial carcinogenesis and a new method for early detection of tumor progression of malignant cell lines derived from human lung cancer using de-epithelialized rat tracheas xenotransplanted into nude

开发人气管支气管癌发生的实验模型以及使用去上皮大鼠气管异种移植到裸体内早期检测源自人肺癌的恶性细胞系肿瘤进展的新方法

基本信息

批准号：
62570630
负责人：
YAMAKAWA Hisami
金额：
$ 1.28万
依托单位：
School of Medicine, Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Normal human tracheobronchial epithelial cells obtained by tissue culture from nine donors were used to repopulate de-epithelialized rat tracheas. After reconstruction of rat tracheas transplanted into nude mice, beeswax pellets contained 100ug 7, 12-dimethylbenz[a]anthracene (DMBA) were inserted into those lumina. Epithelial cells from DMBA-treated tracheas were subculturable., whereas epithelial cells from most untreated tracheas were not subculturable. After in vivo treatment with DMBA, those cells did not terminally differentiate even in medium containing 8% serum. Karyotypes from these cells showed considerable aneuploidy. Although these cells did not survive for more than 10 subcultures (42 weeks), this was considerably longer-than the survival of control cells. Because of their longer survival, resistance to serum-induced terminal differentlation and chromosome alterations, they were considered to be phenotypically altered or partially transformed cells produced by in vivo treatment of human cells with a chemical carcinogen.The human lung tumor-derived three adenocarcinoma cell lines which were established in this project were also inoculated into de-epithelialized rat tracheas, and xenotransplanted into nude mice. At early stage of cell proliferations, three different cell types which were bronchial surface epithelium-like, clara cell-like, and goblet cell-like were observed and three preneoplastic lesions which were tubular, papillar, and cribriform progressions were also observed respectively.In this "In Vivo Culture System", the process of human tracheobronchial carcinogenesis and very early stage of cancer progression in tracheobrochial epithelium will be possively observed in our further study. These investigations will also make it possible earlyer and more accurate detection of tracheobronchial carcinoma clinically.

正常人气管支气管上皮细胞从9个捐助者获得的组织培养用于再填充去上皮大鼠气管。将大鼠气管移植到裸鼠体内后，将含有100 μ g 7，12-二甲基苯并[a]蒽（DMBA）的蜂蜡颗粒植入气管腔内。DMBA处理气管的上皮细胞可传代培养，而来自大多数未处理的气管的上皮细胞不能传代培养。在体内用DMBA处理后，即使在含有8%血清的培养基中，这些细胞也没有终末分化。这些细胞的染色体组型显示出相当大的非整倍性。虽然这些细胞没有存活超过10次传代培养（42周），这是相当长的时间比对照细胞的生存。本课题建立的人肺腺癌细胞系、人肺腺癌细胞系、人在细胞增殖的早期阶段，观察到三种不同的细胞类型，即支气管表面上皮样细胞、clara细胞样细胞和杯状细胞，还观察到三种癌前病变，分别为管状、乳头状和筛状进展。我们将积极观察人气管支气管上皮癌变过程和癌进展的早期阶段，进一步研究这些研究也将使临床上更早、更准确地发现气管支气管癌成为可能。