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Pancreatic adenocarcinoma upregulated factor (PAUF) overexpressed in pancreatic ductal adenocarcinoma (PDAC) plays a major role in tumor progression and metastasis by autocrine and paracrine manners. However, underlying molecular mechanism of PAUF functioning in pancreatic cancer are not fully understood yet. The objective of this study was to evaluate the potential of demilune cell and parotid protein 1 (DCPP1) as a putative mouse ortholog of human PAUF by sequence alignment and functional studies. Overexpression of mouse DCPP1 in Chinese hamster ovary (CHO) cells or pancreatic cancer cells increased cell proliferation, migration, invasion, and adhesion ability in vitro. Treatment of human pancreatic cancer cells with recombinant mouse DCPP1 elevated cell growth, motility, invasiveness, and adhesiveness. Mouse DCPP1 exerted its function on pancreatic cancer cells by activating intracellular signaling pathways involved in aggressive cancer phenotype of human pancreatic cancer cells. Moreover, subcutaneous injection of mice with DCPP1-overexpressing CHO cells increased tumor sizes. Taken together, we conclude that mouse DCPP1 is a multifunctional promoter of tumor growth through functional activation of pancreatic cancer cells, suggesting it to be an ortholog of human PAUF., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31(+) vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models., (Copyright © 2014 Elsevier Inc. All rights reserved.)