Establishment and Characterization of a Cancer Cell Line Derived From an Aggressive Childhood Liver Tumor
Establishment and Characterization of a Cancer Cell Line Derived From an Aggressive Childhood Liver Tumor
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DOI：
10.1002/pbc.22187
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发表时间：
2009-12-01
影响因子：
3.2
通讯作者：
Tomlinson, Gail E.
中科院分区：
文献类型：
--
作者：
Chen, Tina T. -L.;Rakheja, Dinesh;Tomlinson, Gail E.
背景。肝母细胞瘤是一种罕见的儿童恶性肿瘤。足够的细胞模型的缺乏限制了我们对这种肿瘤的理解。在这里，我们描述并表征了一种新的人类肝脏肿瘤细胞系 Hep293TT，该细胞系源自侵袭性儿童肝母细胞瘤。程序。 Hep293TT 细胞是利用一名 5 岁白人女童的原发肿瘤组织建立的。该细胞系已维持超过 34 个月并进行了 20 多次传代培养，并通过组织病理学、ELISA、基因型、细胞遗传学、CGH 阵列、免疫组织化学和分子序列分析进行了表征。结果。细胞被证实源自亲本肿瘤细胞，分泌甲胎蛋白，并表达肝标记物和β-连环蛋白。 Hep293TT 细胞能够在软琼脂中形成集落。通过在免疫缺陷小鼠中肾囊下注射后诱导实体瘤来证明致瘤性。 Hep293TT 细胞表现出高度非整倍体核型，全基因组 CGH 分析揭示了每条染色体的染色体失衡。等位基因型分析表明远端 11p15.5 等位基因丢失，这是胚胎肿瘤的典型特征。 Hep293TT 细胞和原发肿瘤的 β-连环蛋白均含有 351 个核苷酸的缺失，正如在其他肝母细胞瘤肿瘤中所见。该细胞系表达全长和部分缺失形式的β-连环蛋白，并表达成肝细胞特有的NOTCH2蛋白。 APC、MYH、MLH1 或 MSH2 基因未检测到突变。结论。该细胞系 Hep293TT 是研究儿童肝癌的宝贵资源，并可能为开发新药物提供潜在的工具。儿科血癌 2009；53：1040-1047。 (C) 2009 Wiley-Liss, Inc.
Background. Hepatoblastoma is a rare malignancy of childhood. The scarcity of adequate cell models has limited Our understanding of this tumor. Here we describe and characterize a new human liver tumor cell line, Hep293TT, derived from an aggressive childhood hepatoblastoma. Procedures. Hep293TT cells were established using primary tumor tissues from a 5-year-old Caucasian female child. This cell line has been maintained for more than 34 months and over 20 Subcultures, and was characterized by histopathology, ELISA, genotype, cytogenetics, CGH array, immunohistochemistry, and molecular sequence analyses. Results. Cells were confirmed to originate from parental tumor cells, secrete alpha-fetoprotein, and express hepatic markers and beta-catenin. Hep293TT cells were able to form colonies in soft agar. Tumorigenicity was demonstrated by induction of solid tumors after subrenal capsule injection in immunodeficient mice. Hep293TT cells demonstrated a highly aneuploid karyotype, and a whole genome CGH analysis revealed chromosomal imbalances in every chromosome. Allelotype analysis demonstrated loss of alleles at distal 11p15.5 as is typical of embryonal tumors. Both Hep293TT cells and the primary tumor contain a deletion of 351 nucleotides in beta-catenin, as has been seen in other hepatoblastoma tumors. The cell line expressed beta-catenin protein in both full-length and partially deleted forms, and expressed NOTCH2 protein characteristic of hepatoblasts. No mutation was detected in the APC, MYH, MLH1, or MSH2 genes. Conclusion. This cell line, Hep293TT, is a valuable resource for the study of childhood liver cancer and may potentially provide a tool in the development of new agents. Pediatr Blood Cancer 2009;53:1040-1047. (C) 2009 Wiley-Liss, Inc.