转化生长因子及受体在实验性大鼠肝细胞性肝癌与胆管细胞性肝癌间质差异形成过程中的作用

The significance of TGFβ and its receptor on the difference of stroma formation in experimental rat hepatocellular carcinoma and cholangiocarcinoma

目的 了解胆管细胞性肝癌 (CC)的间质量明显多于肝细胞性肝癌 (HC)的形成机制。方法 原位分子杂交法检测 3′ 甲基 4 二甲基偶氮苯诱发肝癌模型中转化生长因子 (TGF) β1、2、3及其Ⅱ型受体 (TβRⅡ )mRNA的表达 ,探讨TGFβ及TβRⅡ在CC与HC间质差异形成过程中的作用。 结果 CC形成过程中增生、不典型增生的胆管细胞、CC细胞及上述病变中的肌成纤维细胞内TGFβ1和TβRⅡmRNA的表达明显多于肝细胞的同类病变 ,上述mRNA的表达部位与细胞外胶原的沉积区域相一致。结论 增生、不典型增生胆管或CC细胞与间质肌成纤维细胞产生的TGFβ可能通过旁分泌与自分泌作用于肌成纤维细胞的TβR ,刺激后者增生、生成胶原 ,造成HC与CC的间质差异。

Cholangiocarcinoma (CC) generally has more stroma than that of the hepatocellular carcinoma (HC), but its pathogenesis is unknown. The expression of transforming growth factor (TGF)β 1,β 2,β 3 and TGFβ type Ⅱ receptor (TβRⅢ) mRNA in liver tissues from 3′ Me DAB treated rat liver cancer model was examined with in situ hybridization, to investigate the significance of TGFβ and TGFβR in the difference of stromal formation. During CC induction, the expression of TGFβ 1 and TGFβR mRNA in proliferative, dysplastic bile duct cells and CC cells as well as stromal myofibroblasts within these lesions were obviously stronger than that of hepatocytic hyperplasia, dysplasia and HC. The distribution of the mRNA expression was in accordance with deposition of extracellular collagen. TGFβ produced by proliferative and dysplastic bile duct cells, CC cells and stomal myofibroblasts might stimulate the TGFβR on myofibroblasts, resulted in proliferation of the myofibroblasts and its collagen production through autocrine and paracrine secretion, and resulted in the stromal difference between CC and HC.