Koukoulis G K, Shen J, Virtanen I, Gould V E
Department of Pathology, Rush Medical College, Chicago, IL 60612, USA.
Ultrastruct Pathol. 1995 Jan-Feb;19(1):37-43. doi: 10.3109/01913129509014601.
Cellular (c) fibronectins (Fn) differ biochemically, immunologically, and functionally from plasma fibronectins (pFn). Most existing data on Fn distribution in the normal and diseased liver require revision because those studies were based on reagents that did not distinguish pFn from cFn and predated the development of specific cFn monoclonal antibodies (Mabs). We immunostained cryosections of normal adult livers (n = 5), cirrhotic livers (n = 20), and livers with hepatocellular carcinoma (HCC) (n = 10) by the avidin-biotin-complex method with specific Mabs to the extradomains A and B (EDA, EDB) and oncofetal (Onc) isoforms of cFn. Selected samples were stained with an antiserum to pFn; fetal livers served as controls. Normal and cirrhotic livers showed EDA-cFn staining in the portal, septal, and perisinusoidal matrix; its distribution was more restricted than that of pFn. In cirrhosis, EDA-cFn reactions were strongest at sites of piecemeal necrosis and around proliferating ductules in biliary cirrhosis. EDA-cFn reactions were consistently most intense in the matrix of HCC. Distinct from adult normal and cirrhotic livers, reactions for EDB- and Onc-cFn were noted exclusively in most cases of HCC. We conclude that the only cFn isoform indigenous to the normal adult liver matrix is EDA-cFn. Enhanced EDA-cFn in cirrhotic livers may serve as indicator of active stromal remodeling. The restriction of EDB- and Onc-cFn to a large subset of HCC and the putative role of cFn in modulating cell-matrix adhesive interactions would suggest that the emergence of these molecules may be related to the variably invasive and metastatic properties of these tumors.
细胞型（c）纤连蛋白（Fn）在生化、免疫和功能方面与血浆纤连蛋白（pFn）不同。大多数现有的关于Fn在正常和患病肝脏中分布的数据需要修订，因为那些研究是基于无法区分pFn和cFn的试剂，并且早于特异性cFn单克隆抗体（Mab）的开发。我们使用针对cFn的A和B额外结构域（EDA、EDB）以及癌胚（Onc）亚型的特异性Mab，通过抗生物素蛋白-生物素复合物方法对正常成人肝脏（n = 5）、肝硬化肝脏（n = 20）和肝细胞癌（HCC）肝脏（n = 10）的冰冻切片进行免疫染色。选择的样本用抗pFn抗血清染色；胎儿肝脏作为对照。正常和肝硬化肝脏在门静脉、间隔和窦周基质中显示EDA-cFn染色；其分布比pFn更局限。在肝硬化中，EDA-cFn反应在碎片状坏死部位和胆汁性肝硬化中增生的胆小管周围最强。EDA-cFn反应在HCC基质中始终最为强烈。与成人正常和肝硬化肝脏不同，EDB-和Onc-cFn反应仅在大多数HCC病例中观察到。我们得出结论，正常成人肝脏基质中唯一的cFn亚型是EDA-cFn。肝硬化肝脏中EDA-cFn的增强可能作为活跃基质重塑的指标。EDB-和Onc-cFn在大部分HCC中的局限性以及cFn在调节细胞-基质黏附相互作用中的假定作用表明，这些分子的出现可能与这些肿瘤的不同侵袭性和转移性有关。
