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Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer
Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in mal...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893983/ https://www.ncbi.nlm.nih.gov/pubmed/33053268 http://dx.doi.org/10.1111/cas.14689 |
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author | Jinno, Naruomi Yoshida, Michihiro Hayashi, Kazuki Naitoh, Itaru Hori, Yasuki Natsume, Makoto Kato, Akihisa Kachi, Kenta Asano, Go Atsuta, Naoki Sahashi, Hidenori Kataoka, Hiromi |
author_facet | Jinno, Naruomi Yoshida, Michihiro Hayashi, Kazuki Naitoh, Itaru Hori, Yasuki Natsume, Makoto Kato, Akihisa Kachi, Kenta Asano, Go Atsuta, Naoki Sahashi, Hidenori Kataoka, Hiromi |
author_sort | Jinno, Naruomi |
collection | PubMed |
description | Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX‐LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. In a PDAC peritoneal dissemination mouse model, the amount of ATX was significantly higher in ascites than in serum. An in vitro study using two PDAC cell lines, AsPC‐1 and PANC‐1, showed that ATX‐LPA signaling promoted cancer cell migration via the activation of the downstream signaling, and this increased cell migration was suppressed by an ATX inhibitor, PF‐8380. An in vivo study showed that PF‐8380 suppressed peritoneal dissemination and decreased malignant ascites, and these results were validated by the biological analysis as well as the in vitro study. Moreover, there was a positive correlation between the amount of ATX in ascites and the degree of disseminated cancer progression. These findings demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC. |
format | Online Article Text |
id | pubmed-7893983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78939832021-03-02 Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer Jinno, Naruomi Yoshida, Michihiro Hayashi, Kazuki Naitoh, Itaru Hori, Yasuki Natsume, Makoto Kato, Akihisa Kachi, Kenta Asano, Go Atsuta, Naoki Sahashi, Hidenori Kataoka, Hiromi Cancer Sci Original Articles Peritoneal dissemination and malignant ascites in pancreatic ductal adenocarcinoma (PDAC) patients represent a major clinical issue. Lysophosphatidic acid (LPA) is a lipid mediator that modulates the progression of various cancers. Based on the increasing evidence showing that LPA is abundant in malignant ascites, we focused on autotaxin (ATX), which is a secreted enzyme that is important for the production of LPA. This study aimed to elucidate the importance of the ATX‐LPA axis in malignant ascites in PDAC and to determine whether ATX works as a molecular target for treating peritoneal dissemination. In a PDAC peritoneal dissemination mouse model, the amount of ATX was significantly higher in ascites than in serum. An in vitro study using two PDAC cell lines, AsPC‐1 and PANC‐1, showed that ATX‐LPA signaling promoted cancer cell migration via the activation of the downstream signaling, and this increased cell migration was suppressed by an ATX inhibitor, PF‐8380. An in vivo study showed that PF‐8380 suppressed peritoneal dissemination and decreased malignant ascites, and these results were validated by the biological analysis as well as the in vitro study. Moreover, there was a positive correlation between the amount of ATX in ascites and the degree of disseminated cancer progression. These findings demonstrated that ATX in ascites works as a promotor of peritoneal dissemination, and the targeting of ATX must represent a useful and novel therapy for peritoneal dissemination of PDAC. John Wiley and Sons Inc. 2020-12-21 2021-02 /pmc/articles/PMC7893983/ /pubmed/33053268 http://dx.doi.org/10.1111/cas.14689 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Jinno, Naruomi Yoshida, Michihiro Hayashi, Kazuki Naitoh, Itaru Hori, Yasuki Natsume, Makoto Kato, Akihisa Kachi, Kenta Asano, Go Atsuta, Naoki Sahashi, Hidenori Kataoka, Hiromi Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
title | Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
title_full | Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
title_fullStr | Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
title_full_unstemmed | Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
title_short | Autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
title_sort | autotaxin in ascites promotes peritoneal dissemination in pancreatic cancer |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893983/ https://www.ncbi.nlm.nih.gov/pubmed/33053268 http://dx.doi.org/10.1111/cas.14689 |
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