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Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis
mPGES-1 (microsomal prostaglandin E synthase-1) is a stimulus-inducible enzyme that functions downstream of COX (cyclo-oxygenase)-2 in the PGE(2) (prostaglandin E(2))-biosynthesis pathway. Although COX-2-derived PGE(2) is known to play a role in the development of various tumours, the involvement of...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Portland Press Ltd.
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825730/ https://www.ncbi.nlm.nih.gov/pubmed/19845504 http://dx.doi.org/10.1042/BJ20090045 |
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author | Kamei, Daisuke Murakami, Makoto Sasaki, Yuka Nakatani, Yoshihito Majima, Masataka Ishikawa, Yukio Ishii, Toshiharu Uematsu, Satoshi Akira, Shizuo Hara, Shuntaro Kudo, Ichiro |
author_facet | Kamei, Daisuke Murakami, Makoto Sasaki, Yuka Nakatani, Yoshihito Majima, Masataka Ishikawa, Yukio Ishii, Toshiharu Uematsu, Satoshi Akira, Shizuo Hara, Shuntaro Kudo, Ichiro |
author_sort | Kamei, Daisuke |
collection | PubMed |
description | mPGES-1 (microsomal prostaglandin E synthase-1) is a stimulus-inducible enzyme that functions downstream of COX (cyclo-oxygenase)-2 in the PGE(2) (prostaglandin E(2))-biosynthesis pathway. Although COX-2-derived PGE(2) is known to play a role in the development of various tumours, the involvement of mPGES-1 in carcinogenesis has not yet been fully understood. In the present study, we used LLC (Lewis lung carcinoma) cells with mPGES-1 knockdown or overexpression, as well as mPGES-1-deficient mice to examine the roles of cancer cell- and host-associated mPGES-1 in the processes of tumorigenesis in vitro and in vivo. We found that siRNA (small interfering RNA) silencing of mPGES-1 in LLC cells decreased PGE(2) synthesis markedly, accompanied by reduced cell proliferation, attenuated Matrigel™ invasiveness and increased extracellular matrix adhesion. Conversely, mPGES-1-overexpressing LLC cells showed increased proliferating and invasive capacities. When implanted subcutaneously into wild-type mice, mPGES-1-silenced cells formed smaller xenograft tumours than did control cells. Furthermore, LLC tumours grafted subcutaneously into mPGES-1-knockout mice grew more slowly than did those grafted into littermate wild-type mice, with concomitant decreases in the density of microvascular networks, the expression of pro-angiogenic vascular endothelial growth factor, and the activity of matrix metalloproteinase-2. Lung metastasis of intravenously injected LLC cells was also significantly less obvious in mPGES-1-null mice than in wild-type mice. Thus our present approaches provide unequivocal evidence for critical roles of the mPGES-1-dependent PGE(2) biosynthetic pathway in both cancer cells and host microenvironments in tumour growth and metastasis. |
format | Text |
id | pubmed-2825730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-28257302010-02-23 Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis Kamei, Daisuke Murakami, Makoto Sasaki, Yuka Nakatani, Yoshihito Majima, Masataka Ishikawa, Yukio Ishii, Toshiharu Uematsu, Satoshi Akira, Shizuo Hara, Shuntaro Kudo, Ichiro Biochem J Research Article mPGES-1 (microsomal prostaglandin E synthase-1) is a stimulus-inducible enzyme that functions downstream of COX (cyclo-oxygenase)-2 in the PGE(2) (prostaglandin E(2))-biosynthesis pathway. Although COX-2-derived PGE(2) is known to play a role in the development of various tumours, the involvement of mPGES-1 in carcinogenesis has not yet been fully understood. In the present study, we used LLC (Lewis lung carcinoma) cells with mPGES-1 knockdown or overexpression, as well as mPGES-1-deficient mice to examine the roles of cancer cell- and host-associated mPGES-1 in the processes of tumorigenesis in vitro and in vivo. We found that siRNA (small interfering RNA) silencing of mPGES-1 in LLC cells decreased PGE(2) synthesis markedly, accompanied by reduced cell proliferation, attenuated Matrigel™ invasiveness and increased extracellular matrix adhesion. Conversely, mPGES-1-overexpressing LLC cells showed increased proliferating and invasive capacities. When implanted subcutaneously into wild-type mice, mPGES-1-silenced cells formed smaller xenograft tumours than did control cells. Furthermore, LLC tumours grafted subcutaneously into mPGES-1-knockout mice grew more slowly than did those grafted into littermate wild-type mice, with concomitant decreases in the density of microvascular networks, the expression of pro-angiogenic vascular endothelial growth factor, and the activity of matrix metalloproteinase-2. Lung metastasis of intravenously injected LLC cells was also significantly less obvious in mPGES-1-null mice than in wild-type mice. Thus our present approaches provide unequivocal evidence for critical roles of the mPGES-1-dependent PGE(2) biosynthetic pathway in both cancer cells and host microenvironments in tumour growth and metastasis. Portland Press Ltd. 2009-12-23 2010-01-15 /pmc/articles/PMC2825730/ /pubmed/19845504 http://dx.doi.org/10.1042/BJ20090045 Text en © 2010 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by-nc/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Kamei, Daisuke Murakami, Makoto Sasaki, Yuka Nakatani, Yoshihito Majima, Masataka Ishikawa, Yukio Ishii, Toshiharu Uematsu, Satoshi Akira, Shizuo Hara, Shuntaro Kudo, Ichiro Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
title | Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
title_full | Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
title_fullStr | Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
title_full_unstemmed | Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
title_short | Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
title_sort | microsomal prostaglandin e synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825730/ https://www.ncbi.nlm.nih.gov/pubmed/19845504 http://dx.doi.org/10.1042/BJ20090045 |
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