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用于以疾病为导向的抗癌药物筛选的人类肿瘤细胞系的形态学和免疫细胞化学特征。

Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen.

作者信息

Stinson S F, Alley M C, Kopp W C, Fiebig H H, Mullendore L A, Pittman A F, Kenney S, Keller J, Boyd M R

机构信息

Laboratory of Drug Discovery Research and Development, National Cancer Institute, Frederick, MD 21702-1201.

出版信息

Anticancer Res. 1992 Jul-Aug;12(4):1035-53.

PMID:1503399
Abstract

A panel of 60 human tumor cell lines is currently being used in the U.S. National Cancer Institute's in vitro anticancer drug screen. The panel is organized into 7 subpanels; 6 leukemia/lymphoma lines comprise one subpanel, and 54 other lines are organized into subpanels representing solid tumors of the central nervous system (CNS), colon, lung, ovaries, kidneys and melanomas. In the present study, the leukemia and lymphoma cell lines were analyzed by flow cytometry for appropriate CD antigens; all but 1 line showed patterns of expression consistent with their reported derivations. The solid tumor lines were characterized individually using morphological and immunocytochemical techniques to determine their relative degrees of representativity for the subpanels within which they are currently grouped. Histological, histochemical and ultrastructural examinations were performed on cell lines grown under identical conventional culture conditions and as xenografts in nude mice. Immunocytochemistry using panels of antibodies raised against 6 types of intermediate filaments, 7 adenocarcinoma-associated antigens, 7 melanoma/neuro-ectodermal-associated antigens, 3 neuroendocrine-associated antigens, 9 urinary tract associated antigens, and 4 markers of muscle differentiation was done on cells grown in monolayer culture. Central nervous system (CNS) cell lines lacked expression of glial fibrillary acidic protein, but all had other features consistent with derivation from glioblastoma. Lines derived from adenocarcinomas of the colon, lung and ovary, for the most part, expressed adenocarcinoma-associated antigens and showed histological and/or ultrastructural evidence of gland formation and other adenomatous features. Most of these lines were poorly differentiated. Lines derived from large-cell and squamous-cell cancers also showed some characteristics consistent with their reported origins, except for one line which showed immunocytochemical and morphologic characteristics consistent with rhabdomyosarcoma. The 2 lines derived from small cell lung cancer (SCLC) lacked neurosecretory granules and 3 other SCLC markers but showed morphologic features consistent with SCLC. Most melanoma cell lines strongly expressed melanoma-associated antigens and were morphologically similar to human melanoma. Five lines produced premelanosomes, melanosomes or melanin. Most of the renal cancer cell lines showed morphologic or immunocytochemical features consistent with renal clear cell carcinoma. Collectively, these morphological and immunocytochemical analyses provide information concerning tissue of origin, tumor type, degree of differentiation and other biologic features essential to the use of these lines in a disease-oriented in vitro antitumor drug screen and to the interpretation of data derived therefrom.

摘要

美国国立癌症研究所的体外抗癌药物筛选目前正在使用一组60种人类肿瘤细胞系。该细胞系分为7个亚组;6种白血病/淋巴瘤细胞系组成一个亚组,另外54种细胞系被分为亚组,分别代表中枢神经系统(CNS)、结肠、肺、卵巢、肾脏的实体瘤以及黑色素瘤。在本研究中,通过流式细胞术分析白血病和淋巴瘤细胞系的合适CD抗原;除1个细胞系外,所有细胞系的表达模式与其报道的来源一致。使用形态学和免疫细胞化学技术分别对实体瘤细胞系进行表征,以确定它们在当前所属亚组中的相对代表性程度。对在相同常规培养条件下生长的细胞系以及在裸鼠体内作为异种移植生长的细胞系进行组织学、组织化学和超微结构检查。使用针对6种中间丝、7种腺癌相关抗原、7种黑色素瘤/神经外胚层相关抗原、3种神经内分泌相关抗原、9种泌尿系统相关抗原以及4种肌肉分化标志物产生的抗体组进行单层培养细胞的免疫细胞化学检测。中枢神经系统(CNS)细胞系缺乏胶质纤维酸性蛋白的表达,但均具有与胶质母细胞瘤来源一致的其他特征。源自结肠、肺和卵巢腺癌的细胞系,在很大程度上表达腺癌相关抗原,并显示出腺体形成和其他腺瘤特征的组织学和/或超微结构证据。这些细胞系大多分化不良。源自大细胞癌和鳞状细胞癌的细胞系也显示出一些与其报道来源一致的特征,但有一个细胞系显示出与横纹肌肉瘤一致的免疫细胞化学和形态学特征。源自小细胞肺癌(SCLC)的2个细胞系缺乏神经分泌颗粒和其他3种SCLC标志物,但显示出与SCLC一致的形态学特征。大多数黑色素瘤细胞系强烈表达黑色素瘤相关抗原,并且在形态上与人类黑色素瘤相似。5个细胞系产生前黑素体、黑素体或黑色素。大多数肾癌细胞系显示出与肾透明细胞癌一致的形态学或免疫细胞化学特征。总体而言,这些形态学和免疫细胞化学分析提供了有关起源组织、肿瘤类型、分化程度以及其他生物学特征的信息,这些信息对于在以疾病为导向的体外抗肿瘤药物筛选中使用这些细胞系以及解释从中获得的数据至关重要。

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