Nakatsukasa H, Evarts R P, Hsia C C, Marsden E, Thorgeirsson S S
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Lab Invest. 1991 Nov;65(5):511-7.
Cellular distribution of both transcripts and protein of transforming growth factor (TGF)-beta 1 was studied in preneoplastic nodules (6 cases) and primary hepatic carcinomas (16 hepatocellular carcinomas and 2 mixed tumors of hepatocellular carcinoma and cholangiocellular carcinoma) produced by Solt-Farber's protocol in rats using in situ hybridization and immunohistochemistry. The TGF-beta 1 transcripts were primarily observed in nonparenchymal cells, some of which were desmin-positive perisinusoidal cells, surrounding or within the preneoplastic nodules or carcinomas. The distribution of latent TGF-beta 1 protein was similar to the transcripts. However, mature TGF-beta 1, which was identified with CC-antibody, was only detected in nonparenchymal cells and connective tissue associated with carcinomas, but was not observed in preneoplastic nodules or in normal liver with the exception of the periportal space. There was no difference in TGF-beta 1 expression associated with tumor types or the differentiation status of primary hepatic carcinomas. The present study demonstrates that nonparenchymal cells, particularly desmin-positive perisinusoidal cells, are the principal source of TGF-beta 1 production during hepatocarcinogenesis. Furthermore, the data suggest that the close interaction between nonparenchymal cells and carcinoma cells may be necessary for the activation of latent TGF-beta 1. It is hypothesized that regulatory effects of TGF-beta 1 on growth of preneoplastic or carcinoma cells in the liver are exerted via paracrine mechanism.
采用原位杂交和免疫组织化学方法，对用索尔-法伯（Solt-Farber）方案诱导大鼠产生的癌前结节（6例）以及原发性肝癌（16例肝细胞癌和2例肝细胞癌与胆管细胞癌的混合瘤）中转化生长因子（TGF）-β1的转录本和蛋白的细胞分布进行了研究。TGF-β1转录本主要在非实质细胞中观察到，其中一些是波形蛋白阳性的肝血窦周细胞，位于癌前结节或癌灶周围或内部。潜伏性TGF-β1蛋白的分布与转录本相似。然而，用CC抗体鉴定的成熟TGF-β1仅在与癌相关的非实质细胞和结缔组织中检测到，在癌前结节或正常肝脏中除汇管区周围间隙外均未观察到。TGF-β1表达与肿瘤类型或原发性肝癌的分化状态无关。本研究表明，非实质细胞，特别是波形蛋白阳性的肝血窦周细胞，是肝癌发生过程中TGF-β1产生的主要来源。此外，数据表明非实质细胞与癌细胞之间的密切相互作用可能是潜伏性TGF-β1激活所必需的。据推测，TGF-β1对肝脏癌前或癌细胞生长的调节作用是通过旁分泌机制发挥的。
