Evidence for Epithelial-Mesenchymal Transition in Adult Human Pancreatic Exocrine Cells
Evidence for Epithelial-Mesenchymal Transition in Adult Human Pancreatic Exocrine Cells
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DOI：
10.1369/jhc.2010.955807
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发表时间：
2010-09-01
影响因子：
3.2
通讯作者：
Hollande, Etienne
中科院分区：
文献类型：
--
作者：
Fanjul, Marjorie;Gmyr, Valery;Hollande, Etienne
研究表明，成年胰腺导管细胞可以去分化并充当胰腺祖细胞。上皮细胞的去分化通常与上皮间质转化（EMT）相关。在这项研究中，我们在体外和体内研究了成人外分泌胰腺细胞中 EMT 的发生。首先将从脑死亡供体的胰腺中分离的外分泌部分的细胞悬浮培养八天。这导致了球状体的形成，球状体由具有导管样表型的主要细胞群组成。当在组织培养处理的烧瓶中培养时，球状细胞表现出增殖能力，并共表达上皮细胞（细胞角蛋白7和细胞角蛋白-19）和间充质（波形蛋白和α平滑肌肌动蛋白）标记物以及胰腺祖细胞标记物（胰腺十二指肠同源盒因子1）和间充质干细胞的表面标记物。与 Snail1 表达相关的从 E-钙粘蛋白到 N-钙粘蛋白的转变表明这些细胞经历了 EMT。此外，我们在一个正常成人胰腺和三个 2 型糖尿病胰腺的导管细胞中发现上皮和间质标记物的共表达。发现一些波形蛋白阳性细胞共表达胰高血糖素或淀粉酶。这些结果表明EMT的发生，可能发生在人类胰腺组织再生或更新过程中导管细胞去分化时。 (J Histochem Cytochem 58:807-823, 2010)
It has been shown that adult pancreatic ductal cells can dedifferentiate and act as pancreatic progenitors. Dedifferentiation of epithelial cells is often associated with the epithelial-mesenchymal transition (EMT). In this study, we investigated the occurrence of EMT in adult human exocrine pancreatic cells both in vitro and in vivo. Cells of exocrine fraction isolated from the pancreas of brain-dead donors were first cultured in suspension for eight days. This led to the formation of spheroids, composed of a principal population of cells with duct-like phenotype. When cultivated in tissue culture-treated flasks, spheroid cells exhibited a proliferative capacity and coexpressed epithelial (cytokeratin7 and cytokeratin-19) and mesenchymal (vimentin and alpha-smooth muscle actin) markers as well as marker of progenitor pancreatic cells (pancreatic duodenal homeobox factor-1) and surface markers of mesenchymal stem cells. The switch from E-cadherin to N-cadherin associated with Snail1 expression suggested that these cells underwent EMT. In addition, we showed co-expression of epithelial and mesenchymal markers in ductal cells of one normal adult pancreas and three type 2 diabetic pancreases. Some of the vimentin-positive cells were found to coexpress glucagon or amylase. These results point to the occurrence of EMT, which may take place on dedifferentiation of ductal cells during the regeneration or renewal of human pancreatic tissues. (J Histochem Cytochem 58:807-823, 2010)