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...
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Frontiers Media S.A.
2022-05-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.890614/full |
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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 |
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issn | 1663-9812 |
language | English |
last_indexed | 2024-12-12T04:09:50Z |
publishDate | 2022-05-01 |
publisher | Frontiers Media S.A. |
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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 |
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