Trefoil factor 1 stimulates both pancreatic cancer and stellate cells and increases metastasis.
Trefoil factor 1 stimulates both pancreatic cancer and stellate cells and increases metastasis.
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DOI：
10.1097/mpa.0b013e31821f6927
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发表时间：
2011-08
期刊：
影响因子：
2.9
通讯作者：
Logsdon CD
中科院分区：
文献类型：
--
作者：
Arumugam T;Brandt W;Ramachandran V;Moore TT;Wang H;May FE;Westley BR;Hwang RF;Logsdon CD
三叶因子1（TFF 1）是一种稳定的分泌性蛋白，广泛表达于胃肠道粘膜，在胰腺导管腺癌（PDAC）中也有表达。在目前的研究中，我们记录了TFF 1表达的程度和时间，并研究了TFF 1对PDAC细胞和星状细胞（PDAC基质的主要细胞）的影响。三叶因子1在胰腺癌组织和细胞系的表达进行了分析，使用微阵列，定量逆转录聚合酶链反应，免疫组化。使用MTS和Matrigel包被的侵袭室分析重组TFF 1对胰腺癌细胞系和永生化人胰腺星状细胞（HPSC）的细胞生长、迁移和侵袭的影响。还进行了体内研究，其中将稳定表达TFF 1的Mpanc-96细胞原位植入裸鼠中。三叶因子1在癌前病变中高度增加。重组TFF 1刺激癌症和HPSC两者的运动性。相反，TFF 1仅增加HPSC细胞生长。体内研究表明，PDAC细胞中TFF 1的过表达不影响原发肿瘤的生长，但大大增加了转移。目前的数据表明，TFF 1影响PDAC细胞和星状细胞，并刺激转移。
Trefoil factor 1 (TFF1) is a stable secretory protein expressed widely in the gastrointestinal mucosa that is also expressed in pancreatic ductal adenocarcinoma (PDAC). In the current study, we documented the extent and timing of TFF1 expression and investigated the effects of TFF1 on PDAC cells and stellate cells, the primary cells of the PDAC stroma. Trefoil factor 1 expression in pancreatic cancer tissues and cell lines was analyzed using microarray, quantitative reverse transcriptase–polymerase chain reaction, and immunohistochemistry. The effects of recombinant TFF1 on cell growth, migration, and invasion of pancreatic cancer cell lines and immortalized human pancreatic stellate cells (HPSCs) were analyzed using MTS and Matrigel-coated invasion chambers. In vivo studies were also conducted in which Mpanc-96 cells stably expressing TFF1 were implanted orthotopically into nude mice. Trefoil factor 1 was highly increased in preneoplastic lesions. Recombinant TFF1 stimulated motility of both cancer and HPSCs. In contrast, only HPSC cell growth was increased by TFF1. In vivo studies showed that overexpression of TFF1 in PDAC cells did not affect primary tumor growth but greatly increased metastasis. The present data demonstrate that TFF1 influences both PDAC cells and stellate cells and stimulates metastasis.