Park J G, Oie H K, Sugarbaker P H, Henslee J G, Chen T R, Johnson B E, Gazdar A
NCI-Navy Medical Oncology Branch, National Cancer Institute, Bethesda 20814.
Cancer Res. 1987 Dec 15;47(24 Pt 1):6710-8.
We have characterized 14 human colorectal carcinoma cell lines established from primary and metastatic sites by us during the years 1982 to 1985. Five lines were established in fully defined ACL-4 medium and 9 in serum supplemented R10 medium. However, after establishment, cultures could be grown interchangeably in either medium. The lines grew as floating cell aggregates in ACL-4 medium, while most demonstrated substrate adherence in R10 medium. The lines had relatively long doubling times and low cloning efficiencies. Twelve were tumorigenic in athymic nude mice when injected s.c., and two grew i.p. as well. Based on culture, xenograft, and ultrastructural morphologies, the 14 lines could be subtyped as follows: 4 were well differentiated; 5 were moderately differentiated; 4 were poorly differentiated; and 1 was a mucinous carcinoma. Membrane associated antigens characteristic for gastrointestinal cells (carcinoembryonic antigen, CA 19-9, and TAG-72 antigens) were expressed by 50-71% of the lines. Lines expressing carcinoembryonic antigen and CA 19-9 actively secreted these antigens into the supernatant fluids while TAG-72 antigen was not secreted. Surprisingly, 5 of 7 of the original tumor samples tested and 13 of 14 cultured lines expressed L-dopa decarboxylase activity, which is a characteristic enzyme marker of neuroendocrine cells and tumors. In addition, one poorly differentiated cell line contained dense core granules, characteristic of endocrine secretion. Preliminary cytogenetic analyses indicated that 9 of 11 lines examined contained double minute chromosomes. In addition, 3 of the 9 lines with double minutes also had homogeneously staining regions. These findings indicate a high incidence of amplification of one or more as yet unidentified genes.
我们已对1982年至1985年间我们从原发性和转移部位建立的14个人类结肠癌细胞系进行了特征描述。5个细胞系是在完全限定的ACL - 4培养基中建立的,9个是在添加血清的R10培养基中建立的。然而,建立之后,培养物在这两种培养基中均可交替生长。这些细胞系在ACL - 4培养基中以悬浮细胞聚集体的形式生长,而在R10培养基中大多数表现出贴壁生长。这些细胞系具有相对较长的倍增时间和较低的克隆效率。12个细胞系皮下注射到无胸腺裸鼠体内时具有致瘤性,另外2个细胞系腹腔注射也能生长。基于培养、异种移植和超微结构形态,这14个细胞系可分为以下亚型:4个为高分化;5个为中分化;4个为低分化;1个为黏液癌。50% - 71%的细胞系表达胃肠道细胞特有的膜相关抗原(癌胚抗原、CA 19 - 9和TAG - 72抗原)。表达癌胚抗原和CA 19 - 9的细胞系将这些抗原主动分泌到上清液中,而TAG - 72抗原不分泌。令人惊讶的是,所检测的7个原始肿瘤样本中有5个以及14个培养细胞系中有13个表达L - 多巴脱羧酶活性,这是神经内分泌细胞和肿瘤的一种特征性酶标志物。此外,一个低分化细胞系含有致密核心颗粒,这是内分泌分泌的特征。初步细胞遗传学分析表明,所检测的11个细胞系中有9个含有双微体染色体。此外,9个含有双微体的细胞系中有3个还具有均匀染色区。这些发现表明一个或多个尚未鉴定的基因扩增发生率很高。