PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer

Frontiers in Pharmacology

Seong-Yun Jeong¹  Jin Park¹  Sang Seok Koh²  Hyeon Hee Jeong²  Ji Eun Baek²  Seung-Mo Hong³  Fen Jiang⁴  Yeon Jeong Kim⁵ 

[1] Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;Department of Biomedical Sciences, Dong-A University, Busan, South Korea;Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;Department of Pharmacology, Inje University College of Medicine, Busan, South Korea;Innovative Discovery Center, Prestige Biopharma, Busan, South Korea;

关键词: PAUF;    ovarian cancer;    molecular targeted therapy;    monoclonal antibody;    combination chemotherapy;   

DOI  :  10.3389/fphar.2022.890614

来源: DOAJ

【 摘 要 】

Pancreatic adenocarcinoma up-regulated factor (PAUF) plays an important role in tumor growth, metastasis, and immune evasion in the pancreatic tumor microenvironment, and recent studies suggest an association between PAUF expression and poor prognosis in ovarian cancer patients. The current study aimed 1) to characterize the potential tumor-promoting role of PAUF in ovarian cancer, using in vitro and in vivo models, including a PAUF-knockout OVCAR-5 cell line, and 2) to explore the potential therapeutic effects of an anti-PAUF antibody for ovarian cancer. Recombinant PAUF significantly increased tumor metastatic capacity (migration, invasion, and adhesion) in all the ovarian cancer cell lines tested, except for the OVCAR-5 cell line which expresses PAUF at a much higher level than the other cells. PAUF-knockout in the OVCAR-5 cell line led to apparently delayed tumor growth in vitro and in vivo. Furthermore, the administration of an anti-PAUF antibody exhibited notable sensitizing and synchronizing effects on docetaxel in mice bearing the OVCAR-5 xenograft tumors. Taken together, this study shows that the expression level of PAUF is an independent factor determining malignant behaviors of ovarian cancer and, for the first time, it suggests that PAUF may be a promising therapeutic target for high PAUF-expressing ovarian cancer.

【 授权许可】

Unknown