Histopathology Laboratory, Cancer Research UK, London Research Institute, London, UK.
Pancreas. 2012 Aug;41(6):888-96. doi: 10.1097/MPA.0b013e31823c9ec5.
Trefoil factor family (TFF) peptides promote wound healing in the gut. Recent evidence has suggested that TFF3 may be a pancreatic mitogen, an unusual role for TFF peptides. We sought to clarify human pancreatic TFF and mucin expression and performed in vitro experiments to see how pancreatic cell lines respond to TFF3 in particular.
Samples of normal and diseased pancreas (chronic pancreatitis, pancreatic intraepithelial neoplasia, neuroendocrine tumors, and pancreatic ductal adenocarcinoma [PDAC]) were studied by immunohistochemistry and in situ hybridization. Pancreatic cell lines were challenged with TFF2 and TFF3 in wound and migration assays.
In normal islets, colocalization of insulin or glucagon with TFF3 was common. All TFF messenger RNAs were seen in ductal epithelium. Adenocarcinomas expressed all TFF messenger RNAs. Normal ducts were mucin free; MUC5AC was strongest in pancreatic intraepithelial neoplasia and chronic pancreatitis but was reduced in PDAC. TFF2 induced Panc-1 migration and accelerated wound closure in Capan-2 and COLO-357. Double immunohistochemistry for insulin or TFF3 and Ki67 colabeled only very rare islet cells. TFF3-positive PDAC ducts showed some Ki67 colocalization.
No correlation between TFF3 or insulin and Ki67 was seen without ductal hyperplasia. TFF2 may assist pancreatic tumor cell movement, but TFF3 may not be a pancreatic mitogen.
三叶因子家族(TFF)肽促进肠道愈合。最近的证据表明,TFF3 可能是一种胰腺有丝分裂原,这是 TFF 肽的一种不寻常作用。我们试图阐明人类胰腺 TFF 和粘蛋白的表达,并进行了体外实验,以观察胰腺细胞系对 TFF3 的特别反应。
通过免疫组织化学和原位杂交研究了正常和患病胰腺(慢性胰腺炎、胰腺上皮内瘤变、神经内分泌肿瘤和胰腺导管腺癌 [PDAC])的样本。在创伤和迁移实验中,用 TFF2 和 TFF3 挑战胰腺细胞系。
在正常胰岛中,胰岛素或胰高血糖素与 TFF3 的共定位很常见。所有 TFF 信使 RNA 都在导管上皮中可见。腺癌表达所有 TFF 信使 RNA。正常导管无粘蛋白;MUC5AC 在胰腺上皮内瘤变和慢性胰腺炎中最强,但在 PDAC 中减少。TFF2 诱导 Panc-1 迁移,并加速 Capan-2 和 COLO-357 的伤口闭合。胰岛素或 TFF3 和 Ki67 的双重免疫组织化学仅标记非常罕见的胰岛细胞。TFF3 阳性 PDAC 导管显示出一些 Ki67 共定位。
在没有导管增生的情况下,TFF3 或胰岛素与 Ki67 之间没有相关性。TFF2 可能有助于胰腺肿瘤细胞的运动,但 TFF3 可能不是胰腺有丝分裂原。