Antigenic relationship between oval cells and a subpopulation of hepatic foci, nodules, and carcinomas induced by the "resistant hepatocyte" model system.
Antigenic relationship between oval cells and a subpopulation of hepatic foci, nodules, and carcinomas induced by the "resistant hepatocyte" model system.
复制标题
DOI：
--
复制
发表时间：
1991-02
期刊：
影响因子：
11.2
通讯作者：
Ronald A. Faris;B. Monfils;H. A. Dunsford;D. Hixson
中科院分区：
文献类型：
--
作者：
Ronald A. Faris;B. Monfils;H. A. Dunsford;D. Hixson
尽管在化学诱导肝癌的早期阶段经常观察到小导管样细胞（称为卵圆细胞）的增殖，但它们在致癌过程中的作用仍然存在争议。为了研究卵圆细胞可能引起癌前病变并最终进展为肝细胞癌的可能性，我们用一组单克隆抗体进行了表型分析，以确定卵圆细胞与耐药肝细胞模型系统诱导的肝病灶、结节和肿瘤之间是否存在抗原关系。在该模型中，给大鼠注射单剂量（200 毫克/千克）二乙基亚硝胺，然后短暂暴露于 2-乙酰氨基芴并进行部分肝切除术。我们发现，二乙基亚硝胺后 28 天观察到的早期局灶性病变中，约 10% 表达一种或两种卵圆细胞抗原（命名为 OC.2 和 OV-6）。二乙基亚硝胺后 28 周，16 个肝结节中有 16 个异质表达 OV-6，而 5-10% 的持续性结节含有分散的小肝细胞样细胞，表达 OC.2。使用扩展的单克隆抗体组对耐药性肝细胞诱导的原发性肝细胞癌进行检查表明，29 个肿瘤中的 29 个组成的大多数细胞表达 OV-6，并且 15-20% 的 OV-6 阳性肿瘤包含也表达 3 种其他卵圆细胞抗原 OC.2、OC.3 和 OV-1 的细胞亚群。所有检查的肿瘤均表达正常水平的肝细胞抗原 H.1 和 HBD.1，并且 H.2、H.4 和细胞 CAM 105 的水平显着降低，但转铁蛋白受体、γ-谷氨酰转肽酶和正常肝细胞抗原 H.5 的水平升高。总之，我们的研究结果证明了抗性肝细胞模型中卵圆细胞与肝病灶、结节和肿瘤亚群之间的抗原关系，表明至少一些原发性肿瘤可能源自该模型系统中的卵圆细胞。
Although proliferation of small ductular-like cells, designated oval cells, is often observed during the early stages of chemically induced hepatocarcinogenesis, their role during the carcinogenic process remains controversial. To investigate the possibility that oval cells may give rise to preneoplastic lesions that ultimately progress to hepatocellular carcinomas, we have carried out phenotypic analysis with a panel of monoclonal antibodies to determine if there is an antigenic relationship between oval cells and hepatic foci, nodules, and tumors induced by the resistant hepatocyte model system. In this model, rats are given a single dose (200 mg/kg) of diethylnitrosamine, followed by a brief exposure to 2-acetylaminofluorene and a partial hepatectomy. We found that approximately 10% of the early focal lesions observed 28 days after diethylnitrosamine expressed either one or both of the oval cell antigens designated OC.2 and OV-6. By 28 weeks after diethylnitrosamine, 16 of 16 hepatic nodules heterogeneously expressed OV-6 whereas 5-10% of the persistent nodules contained scattered small hepatocyte-like cells that expressed OC.2. Examination of resistant hepatocyte-induced primary hepatocellular carcinomas with an expanded panel of monoclonal antibodies demonstrated that most cells comprising 29 of 29 tumors expressed OV-6 and that 15-20% of the OV-6-positive tumors contained subpopulations of cells also expressing 3 additional oval cell antigens, OC.2, OC.3, and OV-1. All of the tumors examined expressed normal levels of the hepatocyte antigens, H.1 and HBD.1, and had dramatically reduced levels of H.2, H.4, and cell CAM 105 but showed elevated levels of the transferrin receptor, gamma-glutamyltranspeptidase, and the normal hepatocyte antigen, H.5. In conclusion, our findings demonstrate an antigenic relationship between oval cells and a subpopulation of hepatic foci, nodules, and tumors in the resistant hepatocyte model, suggesting that at least some primary tumors may be derived from oval cells in this model system.