Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling.
Pigment Cell Melanoma Res
; 27(4): 611-20, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24725364
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Fator 2 de Crescimento de Fibroblastos
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Comunicação Parácrina
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Fatores de Troca do Nucleotídeo Guanina
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Células Endoteliais da Veia Umbilical Humana
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Melanoma
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Proteínas de Neoplasias
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Neovascularização Patológica
Limite:
Humans
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos