Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Jinno, Naruomi, Yoshida, Michihiro, Hayashi, Kazuki, Naitoh, Itaru, Hori, Yasuki, Natsume, Makoto, Kato, Akihisa, Kachi, Kenta, Asano, Go, Atsuta, Naoki, Sahashi, Hidenori, Kataoka, Hiromi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
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
_version_ 1783653157690146816
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
work_keys_str_mv AT jinnonaruomi autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT yoshidamichihiro autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT hayashikazuki autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT naitohitaru autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT horiyasuki autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT natsumemakoto autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT katoakihisa autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT kachikenta autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT asanogo autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT atsutanaoki autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT sahashihidenori autotaxininascitespromotesperitonealdisseminationinpancreaticcancer
AT kataokahiromi autotaxininascitespromotesperitonealdisseminationinpancreaticcancer