Pediatric Blood & Cancer: Establishment and characterization of a cancer cell line derived from an aggressive childhood liver tumor

Abstract

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 the 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. The 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.

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Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

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