Full metadata record
DC Field | Value | Language |
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dc.creator | Diaz-Valdes, N. (Nancy) | - |
dc.creator | Basagoiti, M. (María) | - |
dc.creator | Dotor, J. (Javier) | - |
dc.creator | Aranda, F. (Fernando) | - |
dc.creator | Monreal, I. (Iñaki) | - |
dc.creator | Riezu-Boj, J.I. (José Ignacio) | - |
dc.creator | Borras-Cuesta, F. (Francisco) | - |
dc.creator | Sarobe, P. (Pablo) | - |
dc.creator | Feijoo, E. (Esperanza) | - |
dc.date.accessioned | 2012-04-04T07:57:24Z | - |
dc.date.available | 2012-04-04T07:57:24Z | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Diaz-Valdes N, Basagoiti M, Dotor J, Aranda F, Monreal I, Riezu-Boj JI, et al. Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression. Cancer Res 2011 Feb 1;71(3):812-821. | es_ES |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://hdl.handle.net/10171/21584 | - |
dc.description.abstract | Melanoma progression is associated with the expression of different growth factors, cytokines, and chemokines. Because TGFβ1 is a pleiotropic cytokine involved not only in physiologic processes but also in cancer development, we analyzed in A375 human melanoma cells, the effect of TGFβ1 on monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) expression, two known factors responsible for melanoma progression. TGFβ1 increased the expression of MCP-1 and IL-10 in A375 cells, an effect mediated by the cross-talk between Smad, PI3K (phosphoinositide 3-kinase)/AKT, and BRAF-MAPK (mitogen activated protein kinase) signaling pathways. Supernatants from TGFβ1-treated A375 cells enhanced MCP-1-dependent migration of monocytes, which, in turn, expressed high levels of TGF,β1, bFGF, and VEGF mRNA. Moreover, these supernatants also inhibited functional properties of dendritic cells through IL-10-dependent mechanisms. When using in vitro, the TGFβ1-blocking peptide P144, TGFβ1-dependent Smad3 phosphorylation, and expression of MCP-1 and IL-10 were inhibited. In vivo, treatment of A375 tumor-bearing athymic mice with P144 significantly reduced tumor growth, associated with a lower macrophage infiltrate and decreased intratumor MCP-1 and VEGF levels, as well as angiogenesis. Finally, in C57BL/6 mice with B16-OVA melanoma tumors, when administered with immunotherapy, P144 decreased tumor growth and intratumor IL-10 levels, linked to enhanced activation of dendritic cells and natural killer cells, as well as anti-OVA T-cell responses. These results show new effects of TGFβ1 on melanoma cells, which promote tumor progression and immunosuppression, strongly reinforcing the relevance of this cytokine as a molecular target in melanoma. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for Cancer Research | es_ES |
dc.rights | info:eu-repo/semantics/closedAccess | - |
dc.subject | Chemokine CCL2/biosynthesis | es_ES |
dc.subject | Interleukin-10/biosynthesis | es_ES |
dc.subject | Melanoma/immunology | es_ES |
dc.subject | Transforming Growth Factor beta1/pharmacology | es_ES |
dc.title | Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | http://cancerres.aacrjournals.org/content/71/3/812 | es_ES |
dc.type.driver | info:eu-repo/semantics/article | es_ES |
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