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Title: A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: 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{sup +} 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 withmore » improved survival in PDAC mouse models.« less
Authors:
 [1] ;  [2] ;  [3] ; ; ; ; ; ; ;  [1] ;  [4] ;  [5] ;  [1] ;  [2]
  1. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)
  4. BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of)
  5. Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416824
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 454; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; CARCINOMAS; CELL PROLIFERATION; COMPARATIVE EVALUATIONS; HUMAN POPULATIONS; IN VIVO; METASTASES; MICE; MONOCLONAL ANTIBODIES; PANCREAS; TUMOR CELLS; VEINS