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源自胸腔积液的五株人恶性间皮瘤细胞系的建立与鉴定

Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions.

作者信息

Manning L S, Whitaker D, Murch A R, Garlepp M J, Davis M R, Musk A W, Robinson B W

机构信息

University Department of Medicine, Sir Charles Gairdner Hospital, Nedlands, W. Australia.

出版信息

Int J Cancer. 1991 Jan 21;47(2):285-90. doi: 10.1002/ijc.2910470219.

DOI:10.1002/ijc.2910470219
PMID:1703129
Abstract

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle-shaped with few vacuoles (JU77, LO68 and ONE58); in 1 line they had a thick, stellate shape with vacuoles (NO36) and in 1 they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeH128 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone-like pattern characteristic of epithelial-type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle-shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeH128 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q21 in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.

摘要

恶性间皮瘤(MM)是一种发生于浆膜腔的侵袭性肿瘤,与接触石棉有关。对这种肿瘤的研究一直受到缺乏充分表征的人MM细胞系的限制。在本研究中,从患有这种恶性肿瘤患者的胸腔积液中建立了5个人MM细胞系。所有5例患者均为男性,已知接触青石棉,未接受过疾病治疗,其诊断通过细胞学、组织学和电子显微镜(EM)得以证实。这些细胞系已培养11至25个月,所有细胞系均传代超过18次。培养的细胞外观极为多样;其中3个细胞系呈纺锤形,几乎没有空泡(JU77、LO68和ONE58);1个细胞系呈厚的星状且有空泡(NO³⁶),另1个细胞系在形状和大小上非常多形,膜不规则且有许多空泡[DeH128(M)]。汇合时,5个细胞系中的3个细胞系呈现上皮型细胞特有的鹅卵石样模式,而另外2个(LO68和ONE58)仍呈纺锤形。所有5个细胞系在汇合时均表现出接触抑制丧失(即堆积)。最短倍增时间差异显著,从18小时(JU77)到超过30小时[DeH128(M)]。细胞学检查显示出特征性的间皮/间皮瘤形态,并且在所有5个细胞系的细胞中均证实有上皮膜抗原(EMA)和细胞角蛋白。这些细胞缺乏癌胚抗原(CEA)和上皮粘蛋白。通过EM很容易证实存在细胞连接、糖原和许多长的、细的、分支的微绒毛。所有细胞系均具有异常核型,众数染色体数从40到80不等。很容易观察到可变的染色体数、大量的结构重排和无法识别的标记染色体;然而,唯一一致的变化是5个细胞系中的4个出现6q21缺失。这5个人培养的MM细胞系的建立现在为体外比较研究MM生物学的几个方面以及筛选新的治疗方式提供了机会。

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