Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft

Chemokines such as monocyte chemoattractant protein (MCP)-1 are key agonists that attract macrophages to tumors. In melanoma, it has been previously shown that variable levels of MCP-1/CCL2 appear to correlate with infiltrating macrophages and tumor fate, with low to intermediate levels of the chemo...

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Autores principales: Gazzaniga, Silvina, Bravo, Alicia I., Guglielmotti, Angelo, Van Rooijen, Nico, Maschi, Fabricio Alejandro, Vecchi, Annunciata, Mantovani, Alberto, Mordoh, José, Wainstok, Rosa
Formato: Articulo
Lenguaje:Inglés
Publicado: 2007
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83061
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id I19-R120-10915-83061
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Veterinarias
Ciencias Médicas
melanoma
tumor
spellingShingle Ciencias Veterinarias
Ciencias Médicas
melanoma
tumor
Gazzaniga, Silvina
Bravo, Alicia I.
Guglielmotti, Angelo
Van Rooijen, Nico
Maschi, Fabricio Alejandro
Vecchi, Annunciata
Mantovani, Alberto
Mordoh, José
Wainstok, Rosa
Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
topic_facet Ciencias Veterinarias
Ciencias Médicas
melanoma
tumor
description Chemokines such as monocyte chemoattractant protein (MCP)-1 are key agonists that attract macrophages to tumors. In melanoma, it has been previously shown that variable levels of MCP-1/CCL2 appear to correlate with infiltrating macrophages and tumor fate, with low to intermediate levels of the chemokine contributing to melanoma development. To work under such conditions, a poorly tumorigenic human melanoma cell line was transfected with an expression vector encoding MCP-1. We found that M2 macrophages are associated to MCP-1<SUP>+</SUP> tumors, triggering a profuse vascular network. To target the protumoral macrophages recruitment and reverting tumor growth promotion, clodronate-laden liposomes (Clod-Lip) or bindarit were administered to melanoma-bearing mice. Macrophage depletion after Clod-Lip treatment induced development of smaller tumors than in untreated mice. Immunohistochemical analysis with an anti-CD31 antibody revealed scarce vascular structures mainly characterized by narrow vascular lights. Pharmacological inhibition of MCP-1 with bindarit also reduced tumor growth and macrophage recruitment, rendering necrotic tumor masses. We suggest that bindarit or Clod-Lip abrogates protumoral-associated macrophages in human melanoma xenografts and could be considered as complementary approaches to antiangiogenic therapy.
format Articulo
Articulo
author Gazzaniga, Silvina
Bravo, Alicia I.
Guglielmotti, Angelo
Van Rooijen, Nico
Maschi, Fabricio Alejandro
Vecchi, Annunciata
Mantovani, Alberto
Mordoh, José
Wainstok, Rosa
author_facet Gazzaniga, Silvina
Bravo, Alicia I.
Guglielmotti, Angelo
Van Rooijen, Nico
Maschi, Fabricio Alejandro
Vecchi, Annunciata
Mantovani, Alberto
Mordoh, José
Wainstok, Rosa
author_sort Gazzaniga, Silvina
title Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
title_short Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
title_full Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
title_fullStr Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
title_full_unstemmed Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
title_sort targeting tumor-associated macrophages and inhibition of mcp-1 reduce angiogenesis and tumor growth in a human melanoma xenograft
publishDate 2007
url http://sedici.unlp.edu.ar/handle/10915/83061
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