Establishment of A Cell Line From A Hepatocellular Carcinoma From A Patient With Hemochromatosis

Abstract

We describe the establishment and characterization of a novel hepatoma cell line. This cell line, designated RBHF‐1, was established from a hepatocellular carcinoma of a 67‐yr‐old man with a history of genetic hemochromatosis. At this writing, the cells have been maintained in RPMI‐1640 tissue‐culture medium and fetal calf serum without any additional supplements for 30 mo. The cells form colonies on soft agar and are not tumorigenic in nude mice. The cell line is polymorphic and displays characteristics of mature hepatocytes by synthesizing albumin, α2‐macroglobulin, fibronectin and α‐fetoprotein. Cytogenetic analysis shows multiple chromosomal aberrations, with a consistent deletion in the long arm and deletions or rearrangements in the short arm of chromosome 1. There is no evidence for hepatitis B or hepatitis C virus infection of the cell line. The cells contain no detectable intracellular iron after staining with Perls' stain. Unlike other hepatoma cell lines, there is no detectable binding of epidermal growth factor to RBHF‐1 cells. This is the first cell line to be established from a patient with hemochromatosis, and it provides a potentially important model for the study of hepatocyte transformation in association with iron overload. (Hepatology 1994;20:74–81.)

α-fetoprotein-producing hepatoma cell lines share common expression profiles of genes in various categories demonstrated by cDNA microarray analysis

“…In addition, other HCC-related genes encoding TGF-␤ 2 and ␣ 2 -macroglobulin were clustered in short distances. [38][39][40] Matrix metalloproteinase 2 (MMP-2), which degrades type IV collagen and laminin, major components of the basement membrane, is up-regulated in hepatoma, and increased expression was associated with tumor dedifferentiation. 41 This gene was also clustered together with the AFP and IGF-II genes, and the Cy5/Cy3 ratios of MMP-2 observed in HepG2 (5.72), Huh7 (1.47), and Hep3B (5.13) were comparable with those of IGF-II observed in these cell lines (7.41, 2.64, 13.12, respectively).…”

“…43 Given that HCC is a typical hypervascular tumor, 51 together with our findings that angiogenetic factor ephrin-A1 is commonly up-regulated in 3 AFP-producing cells, ephrin-A1 may play an important role in hepatocarcinogenesis and disease progression of AFP-positive HCC. AFP, TGF-␤ 2 , ␣ 2 -macroglobulin, NF-IL6, and human common acute lymphoblastic leukemia antigen, which are known to be HCC-related genes, [38][39][40]52,53 were still selected by the criteria adopted in Table 1, while IGF-II and MMP-2 fell from the list in Table 1. Our criteria used for identifying genes might have been too strict and may have failed to select some important genes.…”

Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

“…As early as in the 1960s, Chen [51] establish ed the first human HCC cell line in the world. Later on several HCC cell lines were established [52][53][54][55][56][57][58] . Although most of these showed tumorigenicity when inoculated into experimental animals, rarely did they demonstrate the full potential for loco-regional and distant metastases, as seen so frequently in clinical patients.…”

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

“…Many human HCC cell lines have been established for the studies on etiological factors of HCC, such as hepatitis B virus (HBV) [9][10][11][12][13][14] , hepatitis C virus (HCV) [15] , hemochromatosis [16] , thorotrast [17] , for the study of alpha fetoprotein (AFP) [18,19] , and for other studies [20][21][22][23][24][25][26][27][28][29][30] . Unfortunately, of the above human HCC cell lines, metastatic potential was rarely mentioned or demonstrated.For animal HCC cell lines, the establishment of such cell lines in rat [31] , in woodchuck [32][33][34] , and in chicken [35] have been reported.…”