Spontaneous neoplastic transformation of WB-F344 rat liver epithelial cells
Spontaneous neoplastic transformation of WB-F344 rat liver epithelial cells
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DOI：
10.1016/s0002-9440(10)65705-7
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发表时间：
1998-12-01
影响因子：
6
通讯作者：
Smith, GJ
中科院分区：
文献类型：
--
作者：
Hooth, MJ;Coleman, WB;Smith, GJ
几项研究表明，培养的大鼠肝上皮细胞在体外长期维持融合状态后自发转化。在本研究中，启动低传代WB-F344大鼠肝上皮干细胞样细胞的多个独立谱系，并平行进行自发转化的选择，以确定自发获得致瘤性是否是独立和随机发生的事件（遗传或表观遗传）的结果，或反映亲本WB-F344细胞系内预先存在的改变的表达。WB-F344细胞自发获得致瘤性的时间分析表明，致瘤性表型首次表达的时间、肿瘤形成的频率和延迟以及肿瘤分化存在谱系特异性差异。虽然自发转化的WB-F344细胞产生不同的肿瘤类型（包括肝细胞癌、胆管癌、肝母细胞瘤和成骨肉瘤），但单个谱系产生的肿瘤具有一致和特异的分化模式。这些结果提供了大量的证据表明，在体外选择方案期间，独立转化事件的随机积累是WB-F344细胞自发肿瘤转化的原因。此外，细胞谱系的承诺，一个特定的分化程序是稳定的培养时间和移植部位。这是第一次报道一组相关但独立的大鼠肝上皮细胞系，它们共同产生一系列肿瘤类型，但单独复制一种特定的肿瘤类型。这些细胞系将为研究肝干细胞样细胞分化的分子机制和检查自发转化的大鼠肝上皮细胞系中分子/细胞改变与同基因动物产生肿瘤的能力之间的潜在因果关系提供有价值的试剂。
Several studies have shown that cultured rat liver epithelial cells transform spontaneously after chronic maintenance in a confluent state in vitro. in the present study, multiple independent lineages of low-passage WB-F344 rat Liver epithelial stem-like cells were initiated and subjected in parallel to selection for spontaneous transformation to determine whether spontaneous acquisition of tumorigenicity was the result of events (genetic or epigenetic) that occurred independently and stochastically, or reflected the expression of a pre-existing alteration within the parental WB-F344 cell line. Temporal analysis of the spontaneous acquisition of tumorigenicity by WB-F344 cells demonstrated lineage-specific differences in the time of first expression of the tumorigenic phenotype, frequencies and latencies of tumor formation, and tumor differentiations. Although spontaneously transformed WB-F344 cells produced diverse tumor types (including hepatocellular carcinomas, cholangiocarcinomas, hepatoblastomas, and osteogenic sarcomas), individual Lineages yielded tumors with consistent and specific patterns of differentiation. These results provide substantial evidence that the stochastic accumulation of independent transforming events during the selection regimen in vitro were responsible for spontaneous neoplastic transformation of WB-F344 cells. Furthermore, cell lineage commitment to a specific differentiation program was stable with time in culture and with site of transplantation. This is the first report of a cohort of related, but independent, rat Liver epithelial cell Lines that collectively produce a spectrum of tumor types but individually reproduce a specific tumor type. These cell Lines will provide valuable reagents for investigation of the molecular mechanisms involved in the differentiation of hepatic stem-like cells and for examination of potential causal relationships in spontaneously transformed rat Liver epithelial cell lines between molecular/cellular alterations and the ability to produce tumors in syngeneic animals.