HEPATIC STEM CELL COMPARTMENT AND LIVER TUMORS

肝干细胞区室和肝脏肿瘤

• 批准号: 3874676
• 负责人: S S THORGEIRSSON
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874676
• 关键词: bile ducts; biomarker; carcinogenesis; cell differentiation; cell type; chemical carcinogenesis; deficient growth media; disease /disorder model; embryo /fetus protein; epithelium; gene expression; glutathione transferase; growth inhibitors; growth media; isozymes; laboratory rat; lactate dehydrogenases; liver cells; liver transplantation; molecular oncology; neoplasm /cancer genetics; oncogenes; pancreatic islets; preneoplastic state; stromal cells; tissue /cell culture; transforming growth factors; tumor promoters

Experimental hepatocarcinogenesis in the rat has been used as a model to study the cellular and molecular events during neoplastic development. The research is currently focused on defining the possible role of a stem cell compartment in the liver during oncogenesis as well as in the normal liver (see also Project No. Z01CP05262). The hypothesis that rat liver epithelial (RLE) cells may represent a progeny from a common precursor cell for both hepatocytes and bile epithelium has been explored in vitro by examining the effects of different culture media on the differentiation and lineage commitment of RLE cells. We have shown by using differential expression of cytokeratins with molecular weights of 55,000 D and 52,000 D, vimentin, the placental form of glutathione S-transferase and isoenzymes of lactate dehydrogenase as cellular lineage markers, that the RLE cells in chemically defined medium acquire phenotypic traits of bile epithelium. These data further support the notion that RLE cells may be progenitor cells for both bile duct epithelial and hepatocytic cell lineages in adult rat liver. In order to address questions regarding both transplantability and lineage commitments of RLE cells we are currently introducing a retrovirus encoding the E. coli beta-galactosidase (beta-GAL) gene into these cells prior to hepatic transplantation to obtain an easily detectable single cell marking system. We have recently identified cells morphologically similar to rat liver derived oval cells in hyperplastic and preneoplastic human livers as well as in human hepatocellular carcinomas. These putative human oval cells have small basophilic oval nuclei, scanty clear cytoplasm, and cross-reacted with OV-6 (antibody against rat oval cell). Most of these cells express AFP and/or albumin, and are gamma-GT positive.

大鼠实验性肝癌形成已被用作模型， 研究肿瘤发展过程中的细胞和分子事件。的 目前的研究集中在确定干细胞的可能作用 在肿瘤发生期间以及在正常肝脏中， (see项目编号Z 01 CP 05262）。假设大鼠肝上皮细胞 (RLE)细胞可以代表来自两者共同前体细胞的后代。 肝细胞和胆汁上皮细胞已经在体外进行了研究， 不同培养基对分化和谱系的影响 RLE细胞的承诺。我们已经证明，通过使用微分表达式， 分子量为55，000 D和52，000 D的细胞角蛋白，波形蛋白， 胎盘型谷胱甘肽S-转移酶和乳酸同工酶 脱氢酶作为细胞谱系标志物，RLE细胞在化学上 成分确定的培养基获得胆汁上皮的表型特征。这些数据 这进一步支持了RLE细胞可能是两种细胞的祖细胞的观点。 成年大鼠肝脏中胆管上皮细胞和肝细胞谱系。在 为了解决有关移植性和血统的问题， RLE细胞的承诺，我们目前正在引入逆转录病毒编码 急诊大肠杆菌β-半乳糖苷酶（β-GAL）基因进入这些细胞之前， 肝移植获得易于检测的单细胞标记 系统我们最近鉴定出了与大鼠 在增生和癌前人类肝脏中肝源性卵圆细胞， 以及在人肝细胞癌中。这些假定的人类卵圆细胞 小的嗜碱性卵圆形核，少量透明的细胞质， 与抗大鼠卵圆细胞抗体OV-6交叉反应。大多数这些 细胞表达AFP和/或白蛋白，并且是γ-GT阳性的。