Abstract
ABSTRACTPancreatic cancer is a challenging disease with a high mortality rate. While the importance of crosstalk between cancer and immune cells has been well documented, the understanding of this complex molecular network is incomplete. Thus, identification of the secreted proteins contributing to the immunosuppressive microenvironment in pancreatic cancer is crucial for effective diagnosis and/or therapy. We utilized a public microarray dataset (GSE16515) from the Gene Expression Omnibus database to identify genes for secreted proteins in pancreatic cancer. RT–PCR and ELISA of the pancreatic cancer cell lines validated the cellular origin of the selected genes. For functional assay of the selected proteins, we utilized human-monocyte-derived dendritic cells (DCs). From the list of the secreted proteins, trefoil factor 2 (TFF2) was further examined as a potential chemokine/cytokine. While TFF2 did not significantly affect the phenotypic maturation and the allostimulatory capacity of DCs, TFF2 preferentially attracted immature (but not mature) DCs and inhibited their endocytic activity. Our data suggest that TFF2 from pancreatic cancer cells may attract immature DCs and affect the initial stage of DC maturation, thereby contributing to the induction of immune tolerance against pancreatic cancer.
Highlights
Pancreatic cancer is the fifth leading cause of death from cancer in developed countries
The results shown are from one representative of three independent experiments performed. (B) Enzyme-linked immunosorbent assay (ELISA) detected trefoil factor 2 (TFF2) that had been secreted into the culture medium of human pancreatic cancer cell lines
The majority of molecules that have been identified in this context far are chemokines and cytokines such as VEGF, IL-10, and TGF-β, which impair the function of effector T cells and dendritic cells (DCs) by altering the phenotype or by enhancing spontaneous apoptosis
Summary
Pancreatic cancer is the fifth leading cause of death from cancer in developed countries. With a poor survival rate of approximately 5%, pancreatic cancer has one of the poorest prognoses among all cancers (Warshaw and Fernández-del Castillo 1992; Magee et al 2002). Pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, represents the most lethal type of cancers, with a median survival of 4∼6 months (Saif 2011). This poor survival rate is in part related to pancreatic cancer being generally diagnosed at an advanced stage where effective therapies are lacking. 20% of pancreatic cancer patients are eligible for surgical resection, which currently remains the only potentially curative therapy. The lack of efficient molecular markers that can characterize tumor progression precludes making an effective diagnosis, monitoring prognosis, and identifying the therapeutic target of cancers (Lee et al 2016)
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