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

• Published in: Biochemical and biophysical research communications 2014-11, Vol.454 (1), p.144-150
• Main Authors: Kim, Su Jin, Chang, Suhwan, Lee, Yangsoon, Kim, Na Young, Hwang, Yeonsil, Min, Hye Jin, Yoo, Kyung-Sook, Park, Eun Hye, Kim, Seokho, Chung, Young-Hwa, Park, Young Woo, Koh, Sang Seok
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ANGIOGENESIS; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Neutralizing - administration & dosage; Antibodies, Neutralizing - therapeutic use; Antineoplastic Agents - administration & dosage; beta Catenin - metabolism; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - secondary; Carcinoma, Pancreatic Ductal - therapy; CARCINOMAS; Cell Line, Tumor; CELL PROLIFERATION; Combined Modality Therapy; COMPARATIVE EVALUATIONS; Cyclin D1 - metabolism; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease Progression; Endothelial Cells - pathology; Female; HUMAN POPULATIONS; Humans; IN VIVO; Lectins - antagonists & inhibitors; Lectins - immunology; METASTASES; MICE; Mice, Nude; MONOCLONAL ANTIBODIES; Neovascularization, Pathologic - prevention & control; PANCREAS; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; TUMOR CELLS; VEINS; Xenograft Model Antitumor Assays
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.10.056

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.