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

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 ai...

Full description

Bibliographic Details
Main Authors: Yeon Jeong Kim, Fen Jiang, Jin Park, Hyeon Hee Jeong, Ji Eun Baek, Seung-Mo Hong, Seong-Yun Jeong, Sang Seok Koh
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.890614/full
_version_ 1818206237034020864
author Yeon Jeong Kim
Yeon Jeong Kim
Fen Jiang
Fen Jiang
Jin Park
Hyeon Hee Jeong
Ji Eun Baek
Seung-Mo Hong
Seong-Yun Jeong
Sang Seok Koh
author_facet Yeon Jeong Kim
Yeon Jeong Kim
Fen Jiang
Fen Jiang
Jin Park
Hyeon Hee Jeong
Ji Eun Baek
Seung-Mo Hong
Seong-Yun Jeong
Sang Seok Koh
author_sort Yeon Jeong Kim
collection DOAJ
description 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.
first_indexed 2024-12-12T04:09:50Z
format Article
id doaj.art-d04a90c50a3f488abb8e2b340afcbe39
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-12-12T04:09:50Z
publishDate 2022-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-d04a90c50a3f488abb8e2b340afcbe392022-12-22T00:38:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.890614890614PAUF as a Target for Treatment of High PAUF-Expressing Ovarian CancerYeon Jeong Kim0Yeon Jeong Kim1Fen Jiang2Fen Jiang3Jin Park4Hyeon Hee Jeong5Ji Eun Baek6Seung-Mo Hong7Seong-Yun Jeong8Sang Seok Koh9Department of Biomedical Sciences, Dong-A University, Busan, South KoreaInnovative Discovery Center, Prestige Biopharma, Busan, South KoreaInnovative Discovery Center, Prestige Biopharma, Busan, South KoreaDepartment of Pharmacology, Inje University College of Medicine, Busan, South KoreaAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDepartment of Biomedical Sciences, Dong-A University, Busan, South KoreaDepartment of Biomedical Sciences, Dong-A University, Busan, South KoreaDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South KoreaDepartment of Biomedical Sciences, Dong-A University, Busan, South KoreaPancreatic 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.890614/fullPAUFovarian cancermolecular targeted therapymonoclonal antibodycombination chemotherapy
spellingShingle Yeon Jeong Kim
Yeon Jeong Kim
Fen Jiang
Fen Jiang
Jin Park
Hyeon Hee Jeong
Ji Eun Baek
Seung-Mo Hong
Seong-Yun Jeong
Sang Seok Koh
PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer
Frontiers in Pharmacology
PAUF
ovarian cancer
molecular targeted therapy
monoclonal antibody
combination chemotherapy
title PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer
title_full PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer
title_fullStr PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer
title_full_unstemmed PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer
title_short PAUF as a Target for Treatment of High PAUF-Expressing Ovarian Cancer
title_sort pauf as a target for treatment of high pauf expressing ovarian cancer
topic PAUF
ovarian cancer
molecular targeted therapy
monoclonal antibody
combination chemotherapy
url https://www.frontiersin.org/articles/10.3389/fphar.2022.890614/full
work_keys_str_mv AT yeonjeongkim paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT yeonjeongkim paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT fenjiang paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT fenjiang paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT jinpark paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT hyeonheejeong paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT jieunbaek paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT seungmohong paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT seongyunjeong paufasatargetfortreatmentofhighpaufexpressingovariancancer
AT sangseokkoh paufasatargetfortreatmentofhighpaufexpressingovariancancer