Establishment and characterization of a human intrahepatic cholangiocarcinoma cell line derived from an Italian patient.
Establishment and characterization of a human intrahepatic cholangiocarcinoma cell line derived from an Italian patient.
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源自意大利患者的肝内胆管癌细胞系的建立和表征。
DOI：
10.1007/s13277-015-4215-3
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Leone F
中科院分区：
文献类型：
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作者：
Cavalloni G;Peraldo-Neia C;Varamo C;Casorzo L;Dell'Aglio C;Bernabei P;Chiorino G;Aglietta M;Leone F
胆道癌是一种罕见的恶性肿瘤，具有多种病因，不同的病因构成了不同的遗传和分子特征。癌细胞系是负担得起的模型，反映了肿瘤起源的特征。它们代表了鉴定治疗分子靶点的有用工具。在这里，我们建立了一个意大利肝内胆管癌细胞系（ICC），MT-CHC 01，并从生物学，分子和遗传学的角度进行了表征。从肿瘤来源的异种移植物中分离MT-CHC 01细胞。在早期和稳定传代后评价免疫表型表征。还研究了体外生物学、遗传学和分子特征。在NOD/SCID小鼠中评估体内致瘤性。MT-CHC 01细胞保留上皮细胞标志物EPCAM、CK 7和CK 19，以及一些干细胞和多能性标志物，即，SOX 2、Nanog、CD 49 f/整联蛋白-α6、CD 24、PDX 1、FOXA 2和CD 133。它们生长为单层，种群倍增时间约为40小时;它们表现出低迁移和入侵潜力。在低附着条件下，它们能够形成球体并以锚定独立的方式生长。皮下注射后，它们保留了体内致瘤性;胆管标志物如CA 19 -9和CEA的表达与原发肿瘤保持一致。核型高度复杂，具有亚三倍体至超三倍体众数（3 n +/−）（52至77条染色体）;确定了低水平的HER 2基因扩增、TP 53缺失、AURKA获得;从原发性肿瘤到MT-CHC 01细胞，K-RAS G12 D突变得以维持。我们建立了第一个来自意大利患者的ICC细胞系。这将有助于研究这种肿瘤的生物学或在体外和体内测试药物。本文的在线版本（doi：10.1007/s13277-015-4215-3）包含补充材料，可供授权用户使用。
Biliary tract carcinoma is a rare malignancy with multiple causes, which underlie the different genetic and molecular profiles. Cancer cell lines are affordable models, reflecting the characteristics of the tumor of origin. They represent useful tools to identify molecular targets for treatment. Here, we established and characterized from biological, molecular, and genetic point of view, an Italian intrahepatic cholangiocarcinoma cell line (ICC), the MT-CHC01. MT-CHC01 cells were isolated from a tumor-derived xenograft. Immunophenotypical characterization was evaluated both at early and after stabilization passages. In vitro biological, genetic, and molecular features were also investigated. In vivo tumorigenicity was assessed in NOD/SCID mice. MT-CHC01cells retain epithelial cell markers, EPCAM, CK7, and CK19, and some stemness and pluripotency markers, i.e., SOX2, Nanog, CD49f/integrin-α6, CD24, PDX1, FOXA2, and CD133. They grow as a monolayer, with a population double time of about 40 h; they show a low migration and invasion potential. In low attachment conditions, they are able to form spheres and to growth in anchorage-independent manner. After subcutaneous injection, they retain in vivo tumorigenicity; the expression of biliary markers as CA19-9 and CEA were maintained from primary tumor. The karyotype is highly complex, with a hypotriploid to hypertriploid modal number (3n+/−) (52 to 77 chromosomes); low level of HER2 gene amplification, TP53 deletion, gain of AURKA were identified; K-RAS G12D mutation were maintained from primary tumor to MT-CHC01 cells. We established the first ICC cell line derived from an Italian patient. It will help to study either the biology of this tumor or to test drugs both in vitro and in vivo. The online version of this article (doi:10.1007/s13277-015-4215-3) contains supplementary material, which is available to authorized users.