Trefoil Factor Family 1 (TFF1) Inhibit the Invasion of Tumor Cells of the Pancreas

Abstract

ObjectiveThe tumor suppressive role of TFF has been recently reported in gastric tumorigenesis. Here we aimed to clarify the role of TFF1 as tumor suppressor in pancreatic tumorigenesis.MethodsBy immunohistochemistry, the expression pattern of TFF1 was analyzed in surgically resected specimen of PDAC (Pancreatic Ductal Adenocarcinoma; n=14), invasive IPMN (Intraductal Papillary Mucinous Neoplasms: n=12) and non‐invasive IPMN (n=10). Human pancreatic cancer cell line was treated by TFF1‐siRNA to evaluate the role of TFF1 in vitro.ResultsTFF1 expression is not found in normal pancreatic ductal epithelium. Pancreatic Intraductal Neoplasm (PanIN) has high expression of TFF1, suggesting that up‐regulation of TFF1 is the early event of pancreatic tumorigenesis. While TFF1 is also expressed in the intraductal compartment of PDAC and IPMN, it is frequently lost in the invasive compartment (50% (7/14) in PDAC and 58.3% (7/12) in invasive IPMN). The expressions of TFF1 in human pancreatic cancer cell lines were evaluated and Panc1 was found to have TFF1 mRNA. Suppression of TFF1 in Panc1 cells by siRNA does not change the proliferative rate of Panc1 cells; however, it was found to induce the higher invasive ability (55.2% of invasive area in control, 94.9% in TFF1‐siRNA; p<0.01) by Boyden chamber assay.ConclusionWhile acquisition of TFF1 seems to be the early event of pancreatic tumorigenesis, loss of TFF1 may result in the invasive transformation of pancreatic tumor.