The GCTM-5 Epitope Associated with the Mucin-Like Glycoprotein FCGBP Marks Progenitor Cells in Tissues of Endodermal Origin
The GCTM-5 Epitope Associated with the Mucin-Like Glycoprotein FCGBP Marks Progenitor Cells in Tissues of Endodermal Origin
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DOI：
10.1002/stem.1167
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发表时间：
2012-09-01
期刊：
影响因子：
5.2
通讯作者：
Pera, Martin F.
中科院分区：
文献类型：
--
作者：
Stamp, Lincon A.;Braxton, David R.;Pera, Martin F.
抗细胞表面标志物的单克隆抗体是研究组织再生、修复和肿瘤形成的有力工具，但缺乏鉴定内胚层来源组织中干细胞和祖细胞的特异性试剂。由GCTM-5单克隆抗体定义的表位是肝祖细胞的推定标志物。我们试图进一步分析GCTM-5抗原在正常组织和疾病状态中的分布，并对抗原进行生物化学表征。GCTM-5表位在源自定形内胚层的组织上特异性表达，特别是胎儿肠、肝和胰腺。在正常成人胆管和胰管细胞的亚群中检测到抗体反应性，并且从成人肝脏的非实质部分分离的GCTM-5阳性细胞表达祖细胞的标志物。肝和胰腺中的GCTM-5阳性细胞群在诸如胆道闭锁、肝硬化和胰腺炎的疾病状态中在数量上极大地扩增。在这些组织中产生的肿瘤也表达GCTM-5抗原，特别是胰腺癌显示出强烈和一致的反应性。GCTM-5表位也强烈显示在Barrett食管（食管癌的前体）中经历肠上皮化生的细胞上。生物化学、质谱和免疫化学研究表明，GCTM-5表位与粘蛋白样糖蛋白FCGBP相关。粘蛋白样糖蛋白FCGBP上的GCTM-5表位是用于研究内胚层来源的组织中的正常分化谱系、再生和疾病进展的细胞表面标志物。干细胞2012;30：1999-2009
Monoclonal antibodies against cell surface markers are powerful tools in the study of tissue regeneration, repair, and neoplasia, but there is a paucity of specific reagents to identify stem and progenitor cells in tissues of endodermal origin. The epitope defined by the GCTM-5 monoclonal antibody is a putative marker of hepatic progenitors. We sought to analyze further the distribution of the GCTM-5 antigen in normal tissues and disease states and to characterize the antigen biochemically. The GCTM-5 epitope was specifically expressed on tissues derived from the definitive endoderm, in particular the fetal gut, liver, and pancreas. Antibody reactivity was detected in subpopulations of normal adult biliary and pancreatic duct cells, and GCTM-5-positive cells isolated from the nonparenchymal fraction of adult liver expressed markers of progenitor cells. The GCTM-5-positive cell populations in liver and pancreas expanded greatly in numbers in disease states such as biliary atresia, cirrhosis, and pancreatitis. Neoplasms arising in these tissues also expressed the GCTM-5 antigen, with pancreatic adenocarcinoma in particular showing strong and consistent reactivity. The GCTM-5 epitope was also strongly displayed on cells undergoing intestinal metaplasia in Barrett's esophagus, a precursor to esophageal carcinoma. Biochemical, mass spectrometry, and immunochemical studies revealed that the GCTM-5 epitope is associated with the mucin-like glycoprotein FCGBP. The GCTM-5 epitope on the mucin-like glycoprotein FCGBP is a cell surface marker for the study of normal differentiation lineages, regeneration, and disease progression in tissues of endodermal origin. STEM CELLS 2012;30:1999-2009