Stamatoglou S C, Manson M M, Green J A, Mayol X, Hughes R C
National Institute for Medical Research, Mill Hill, London, UK.
J Cell Sci. 1991 Nov;100 ( Pt 3):599-604. doi: 10.1242/jcs.100.3.599.
We have used single- and double-label immunocytochemistry to examine the distribution of AGp110, integrin alpha 5 beta 1 and fibronectin in adult rat liver during carcinogenesis induced by aflatoxin B1 or diethylnitrosamine. In normal liver fibronectin and the fibronectin integrin receptor alpha 5 beta 1 are localized on all three domains of the parenchymal cell surface: sinusoidal, lateral and canalicular. In contrast, AGp110, a non-integrin monomeric glycoprotein with fibronectin receptor properties, is confined to the bile canalicular (apical) plasma membrane of hepatocytes. Hepatocarcinogenesis induced by aflatoxin B1 causes altered cell foci to form in the parenchyma, followed by enlargement of these foci to form pre-neoplastic nodules and finally hepatocellular carcinomas of either poorly differentiated, trabecular or adenocarcinoma morphology. Expression of AGp110 decreased to a minimal level, at first selectively in altered cell foci, from the 9th week of treatment, and then indiscriminately in poorly differentiated carcinomas. The same lesions that were deficient in AGp110 also displayed a reduced level of fibronectin and alpha 5 beta 1, although the observed change in AGp110 demarcated altered foci and poorly differentiated tumour lesions more sharply, since expression of alpha 5 beta 1 and fibronectin, though substantially reduced, was still faintly apparent on the cell surface. Small acinar structures, observed in late hyperplastic nodules and in trabecular carcinomas, exhibited even, pericellular staining of fibronectin and alpha 5 beta 1, including prominent staining of the lumen area, whereas staining of AGp110 appeared to be confined to the lumen. In larger ducts of overt adenocarcinomas, fibronectin and alpha 5 beta 1 were distributed along the basal surface of the epithelium and AGp110 on the apical domain.(ABSTRACT TRUNCATED AT 250 WORDS)
我们运用单标记和双标记免疫细胞化学方法，检测黄曲霉毒素B1或二乙基亚硝胺诱导成年大鼠肝脏癌变过程中AGp110、整合素α5β1和纤连蛋白的分布情况。在正常肝脏中，纤连蛋白和纤连蛋白整合素受体α5β1定位于实质细胞表面的三个区域：窦状、侧面和胆小管。相比之下，AGp110是一种具有纤连蛋白受体特性的非整合素单体糖蛋白，局限于肝细胞的胆小管（顶端）质膜。黄曲霉毒素B1诱导的肝癌发生导致实质中形成细胞灶改变，随后这些病灶扩大形成癌前结节，最终形成低分化、小梁状或腺癌形态的肝细胞癌。从治疗第9周开始，AGp110的表达首先在细胞灶改变处选择性降低至最低水平，然后在低分化癌中无差别降低。AGp110缺乏的相同病变也显示纤连蛋白和α5β1水平降低，尽管观察到的AGp110变化更清晰地界定了改变的病灶和低分化肿瘤病变，因为α5β1和纤连蛋白的表达虽然大幅降低，但在细胞表面仍隐约可见。在晚期增生性结节和小梁状癌中观察到的小腺泡结构，纤连蛋白和α5β1呈现均匀的细胞周染色，包括管腔区域的显著染色，而AGp110的染色似乎局限于管腔。在明显腺癌的较大导管中，纤连蛋白和α5β1沿上皮基底表面分布，AGp110分布于顶端区域。（摘要截于250字）
