ESTABLISHMENT OF A MURINE MODEL OF MALIGNANT MESOTHELIOMA
ESTABLISHMENT OF A MURINE MODEL OF MALIGNANT MESOTHELIOMA
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DOI：
10.1002/ijc.2910520609
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发表时间：
1992-12-02
影响因子：
6.4
通讯作者：
ROBINSON, BWS
中科院分区：
文献类型：
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作者：
DAVIS, MR;MANNING, LS;ROBINSON, BWS
恶性间皮瘤（MM）是一种侵袭性肿瘤的浆膜腔，这是与以前的石棉接触，并普遍发现是耐传统形式的治疗。由于间皮瘤的发病率相对较低，缺乏代表性的细胞系和动物模型，对这种疾病进行充分的科学和临床评估受到严重限制。本研究的目的是开发石棉诱导的MM小鼠模型，作为体内传代恶性肿瘤和体外建立的细胞系。这种模型系统对于用于研究疾病的各种细胞、分子和遗传方面以及用于潜在治疗剂的临床前评价将是非常宝贵的。BALB/c和CBA小鼠腹腔注射青石棉。暴露后7至25个月，35%的小鼠发生间皮瘤（5只BALB/c，9只CBA），如标准细胞学和组织学参数所确定。从这些原发性肿瘤中，在培养中建立了12个连续生长的细胞系（5个BALB/c，7个CBA）。所有已被证实为间皮瘤细胞学和超微结构（电子显微镜）分析。这些细胞系已培养7至24个月，并已达到32代以上（范围32至106）。与人类疾病一样，小鼠间皮瘤细胞系在形态和生长速率方面各不相同（倍增时间范围为14至30小时）。所有细胞系在注射到同基因小鼠中时都产生了肿瘤。
Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with previous asbestos exposure and is generally found to be resistant to conventional forms of therapy. Adequate scientific and clinical assessment of this disease has been severely limited by the relatively low incidence of mesothelioma and the lack of representative cell lines and animal models. The purpose of this study was to develop an asbestos-induced murine model of MM both as an in vivo-passaged malignancy and as in vitro-established cell lines. Such a model system would be invaluable for use in the study of various cellular, molecular and genetic aspects of the disease, and for the pre-clinical evaluation of potential therapeutic agents. BALB/c and CBA mice were injected intraperitoneally with crocidolite asbestos. Seven to 25 months after exposure, 35% of the mice developed mesothelioma (5 BALB/c, 9 CBA), as determined by standard cytological and histological parameters. From these primary tumours, 12 continuously growing cell lines (5 BALB/c, 7 CBA) were established in culture. All have been confirmed as mesothelioma by cytological and ultrastructural (electron microscopy) analyses. These lines have been in culture for 7 to 24 months and have achieved passages above 32 (range 32 to 106). As in the human disease, the murine mesothelioma lines vary in their morphology and growth rates (doubling times ranging from 14 to 30 hr). All cell lines produced tumours when injected into syngeneic mice.