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Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling

Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell migration. The binding of FGF2 to its receptor requires N-sulfated heparan sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefo...

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Autores principales: Baljinnyam, Erdene, Umemura, Masanari, Chuang, Christine, De Lorenzo, Mariana S, Iwatsubo, Mizuka, Chen, Suzie, Goydos, James S, Ishikawa, Yoshihiro, Whitelock, John M, Iwatsubo, Kousaku
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283731/
https://www.ncbi.nlm.nih.gov/pubmed/24725364
http://dx.doi.org/10.1111/pcmr.12250
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author Baljinnyam, Erdene
Umemura, Masanari
Chuang, Christine
De Lorenzo, Mariana S
Iwatsubo, Mizuka
Chen, Suzie
Goydos, James S
Ishikawa, Yoshihiro
Whitelock, John M
Iwatsubo, Kousaku
author_facet Baljinnyam, Erdene
Umemura, Masanari
Chuang, Christine
De Lorenzo, Mariana S
Iwatsubo, Mizuka
Chen, Suzie
Goydos, James S
Ishikawa, Yoshihiro
Whitelock, John M
Iwatsubo, Kousaku
author_sort Baljinnyam, Erdene
collection PubMed
description Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell migration. The binding of FGF2 to its receptor requires N-sulfated heparan sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefore, we examined whether Epac1 regulates FGF2-mediated cell–cell communication. Conditioned medium (CM) of melanoma cells with abundant expression of Epac1 increased migration of human umbilical endothelial cells (HUVEC) and melanoma cells with poor expression of Epac1. CM-induced increase in migration was inhibited by antagonizing FGF2, by the removal of HS and by the knockdown of Epac1. In addition, knockdown of Epac1 suppressed the binding of FGF2 to FGF receptor in HUVEC, and in vivo angiogenesis in melanoma. Furthermore, knockdown of Epac1 reduced N-sulfation of HS chains attached to perlecan, a major secreted type of HS proteoglycan that mediates the binding of FGF2 to FGF receptor. These data suggested that Epac1 in melanoma cells regulates melanoma progression via the HS–FGF2-mediated cell–cell communication.
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spelling pubmed-42837312015-01-14 Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling Baljinnyam, Erdene Umemura, Masanari Chuang, Christine De Lorenzo, Mariana S Iwatsubo, Mizuka Chen, Suzie Goydos, James S Ishikawa, Yoshihiro Whitelock, John M Iwatsubo, Kousaku Pigment Cell Melanoma Res Original Articles Fibroblast growth factor (FGF2) regulates endothelial and melanoma cell migration. The binding of FGF2 to its receptor requires N-sulfated heparan sulfate (HS) glycosamine. We have previously reported that Epac1, an exchange protein activated by cAMP, increases N-sulfation of HS in melanoma. Therefore, we examined whether Epac1 regulates FGF2-mediated cell–cell communication. Conditioned medium (CM) of melanoma cells with abundant expression of Epac1 increased migration of human umbilical endothelial cells (HUVEC) and melanoma cells with poor expression of Epac1. CM-induced increase in migration was inhibited by antagonizing FGF2, by the removal of HS and by the knockdown of Epac1. In addition, knockdown of Epac1 suppressed the binding of FGF2 to FGF receptor in HUVEC, and in vivo angiogenesis in melanoma. Furthermore, knockdown of Epac1 reduced N-sulfation of HS chains attached to perlecan, a major secreted type of HS proteoglycan that mediates the binding of FGF2 to FGF receptor. These data suggested that Epac1 in melanoma cells regulates melanoma progression via the HS–FGF2-mediated cell–cell communication. BlackWell Publishing Ltd 2014-07 2014-05-09 /pmc/articles/PMC4283731/ /pubmed/24725364 http://dx.doi.org/10.1111/pcmr.12250 Text en © 2014 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Baljinnyam, Erdene
Umemura, Masanari
Chuang, Christine
De Lorenzo, Mariana S
Iwatsubo, Mizuka
Chen, Suzie
Goydos, James S
Ishikawa, Yoshihiro
Whitelock, John M
Iwatsubo, Kousaku
Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling
title Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling
title_full Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling
title_fullStr Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling
title_full_unstemmed Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling
title_short Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling
title_sort epac1 increases migration of endothelial cells and melanoma cells via fgf2-mediated paracrine signaling
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283731/
https://www.ncbi.nlm.nih.gov/pubmed/24725364
http://dx.doi.org/10.1111/pcmr.12250
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