Cargando…

Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer

BACKGROUND: Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit...

Descripción completa

Detalles Bibliográficos
Autores principales: Zong, Liang, Chen, Ke, Jiang, Zhengdong, Chen, Xin, Sun, Liankang, Ma, Jiguang, Zhou, Cancan, Xu, Qinhong, Duan, Wanxing, Han, Liang, Lei, Jianjun, Li, Xuqi, Ma, Qingyong, Wang, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725800/
https://www.ncbi.nlm.nih.gov/pubmed/29228980
http://dx.doi.org/10.1186/s13046-017-0655-5
_version_ 1783285605271076864
author Zong, Liang
Chen, Ke
Jiang, Zhengdong
Chen, Xin
Sun, Liankang
Ma, Jiguang
Zhou, Cancan
Xu, Qinhong
Duan, Wanxing
Han, Liang
Lei, Jianjun
Li, Xuqi
Ma, Qingyong
Wang, Zheng
author_facet Zong, Liang
Chen, Ke
Jiang, Zhengdong
Chen, Xin
Sun, Liankang
Ma, Jiguang
Zhou, Cancan
Xu, Qinhong
Duan, Wanxing
Han, Liang
Lei, Jianjun
Li, Xuqi
Ma, Qingyong
Wang, Zheng
author_sort Zong, Liang
collection PubMed
description BACKGROUND: Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects. However, the role of LXA4 in pancreatic cancer remains to be elucidated. METHODS: Pancreatic cell lines were treated with vehicle or LXA4, and the invasive capacity was then assessed by Transwell assays. The expression of epithelial and mesenchymal markers was determined by western blotting and immunofluorescence. Anti-TGF-β1 neutralizing antibody and exogenous recombinant human TGF-β1 (rhTGF-β1) were used to study the effect of LXA4 on the TGF-β signaling. A liver metastasis model was applied to investigate the effect of LXA4 in vivo. The correlation between the Lipoxin effect score (LES) and the clinical-pathological features of pancreatic cancer was also analyzed. RESULTS: We found that in patients with pancreatic cancer, low LES was correlated with aggressive metastatic potential. The LXA4 activity, which was mediated by the LXA4 receptor FPRL1, could significantly suppress invasion capacity and mesenchymal phenotypes. The expression and autocrine signaling pathway activity of TGF-β1 were also downregulated by LXA4. In the liver metastasis model in nude mice, the stable analog of LXA4, BML-111, could inhibit the metastasis of pancreatic cancer cells. CONCLUSION: Our results demonstrated that LXA4 could reverse mesenchymal phenotypes, which attenuated invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer, which may provide a new strategy to prevent the metastasis of pancreatic cancer.
format Online
Article
Text
id pubmed-5725800
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-57258002017-12-13 Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer Zong, Liang Chen, Ke Jiang, Zhengdong Chen, Xin Sun, Liankang Ma, Jiguang Zhou, Cancan Xu, Qinhong Duan, Wanxing Han, Liang Lei, Jianjun Li, Xuqi Ma, Qingyong Wang, Zheng J Exp Clin Cancer Res Research BACKGROUND: Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects. However, the role of LXA4 in pancreatic cancer remains to be elucidated. METHODS: Pancreatic cell lines were treated with vehicle or LXA4, and the invasive capacity was then assessed by Transwell assays. The expression of epithelial and mesenchymal markers was determined by western blotting and immunofluorescence. Anti-TGF-β1 neutralizing antibody and exogenous recombinant human TGF-β1 (rhTGF-β1) were used to study the effect of LXA4 on the TGF-β signaling. A liver metastasis model was applied to investigate the effect of LXA4 in vivo. The correlation between the Lipoxin effect score (LES) and the clinical-pathological features of pancreatic cancer was also analyzed. RESULTS: We found that in patients with pancreatic cancer, low LES was correlated with aggressive metastatic potential. The LXA4 activity, which was mediated by the LXA4 receptor FPRL1, could significantly suppress invasion capacity and mesenchymal phenotypes. The expression and autocrine signaling pathway activity of TGF-β1 were also downregulated by LXA4. In the liver metastasis model in nude mice, the stable analog of LXA4, BML-111, could inhibit the metastasis of pancreatic cancer cells. CONCLUSION: Our results demonstrated that LXA4 could reverse mesenchymal phenotypes, which attenuated invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer, which may provide a new strategy to prevent the metastasis of pancreatic cancer. BioMed Central 2017-12-11 /pmc/articles/PMC5725800/ /pubmed/29228980 http://dx.doi.org/10.1186/s13046-017-0655-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zong, Liang
Chen, Ke
Jiang, Zhengdong
Chen, Xin
Sun, Liankang
Ma, Jiguang
Zhou, Cancan
Xu, Qinhong
Duan, Wanxing
Han, Liang
Lei, Jianjun
Li, Xuqi
Ma, Qingyong
Wang, Zheng
Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer
title Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer
title_full Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer
title_fullStr Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer
title_full_unstemmed Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer
title_short Lipoxin A4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine TGF-β1 signaling in pancreatic cancer
title_sort lipoxin a4 reverses mesenchymal phenotypes to attenuate invasion and metastasis via the inhibition of autocrine tgf-β1 signaling in pancreatic cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725800/
https://www.ncbi.nlm.nih.gov/pubmed/29228980
http://dx.doi.org/10.1186/s13046-017-0655-5
work_keys_str_mv AT zongliang lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT chenke lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT jiangzhengdong lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT chenxin lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT sunliankang lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT majiguang lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT zhoucancan lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT xuqinhong lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT duanwanxing lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT hanliang lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT leijianjun lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT lixuqi lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT maqingyong lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer
AT wangzheng lipoxina4reversesmesenchymalphenotypestoattenuateinvasionandmetastasisviatheinhibitionofautocrinetgfb1signalinginpancreaticcancer