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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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_0022202X_v127_n8_p2031_Gazzaniga |
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todo:paper_0022202X_v127_n8_p2031_Gazzaniga2023-10-03T14:28:30Z Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft Gazzaniga, S. Bravo, A.I. Guglielmotti, A. Van Rooijen, N. Maschi, F. Vecchi, A. Mantovani, A. Mordoh, J. Wainstok, R. 2 methyl 2 [(1 (phenylmethyl) 1h indazol 3yl)methoxy]propanoic acid clodronic acid monocyte chemotactic protein 1 propionic acid derivative unclassified drug animal cell animal experiment animal model animal tissue article cancer inhibition controlled study expression vector genetic transfection human human cell melanoma mouse nonhuman priority journal tumor associated leukocyte tumor growth tumor necrosis tumor vascularization xenograft Animals Antigens, CD31 Cell Line, Tumor Chemokine CCL2 Clodronic Acid Humans Indazoles Liposomes Macrophages Male Melanoma, Experimental Mice Neoplasm Transplantation Neovascularization, Pathologic Propionic Acids Transplantation, Heterologous 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+ 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. © 2007 The Society for Investigative Dermatology. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0022202X_v127_n8_p2031_Gazzaniga |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
2 methyl 2 [(1 (phenylmethyl) 1h indazol 3yl)methoxy]propanoic acid clodronic acid monocyte chemotactic protein 1 propionic acid derivative unclassified drug animal cell animal experiment animal model animal tissue article cancer inhibition controlled study expression vector genetic transfection human human cell melanoma mouse nonhuman priority journal tumor associated leukocyte tumor growth tumor necrosis tumor vascularization xenograft Animals Antigens, CD31 Cell Line, Tumor Chemokine CCL2 Clodronic Acid Humans Indazoles Liposomes Macrophages Male Melanoma, Experimental Mice Neoplasm Transplantation Neovascularization, Pathologic Propionic Acids Transplantation, Heterologous |
| spellingShingle |
2 methyl 2 [(1 (phenylmethyl) 1h indazol 3yl)methoxy]propanoic acid clodronic acid monocyte chemotactic protein 1 propionic acid derivative unclassified drug animal cell animal experiment animal model animal tissue article cancer inhibition controlled study expression vector genetic transfection human human cell melanoma mouse nonhuman priority journal tumor associated leukocyte tumor growth tumor necrosis tumor vascularization xenograft Animals Antigens, CD31 Cell Line, Tumor Chemokine CCL2 Clodronic Acid Humans Indazoles Liposomes Macrophages Male Melanoma, Experimental Mice Neoplasm Transplantation Neovascularization, Pathologic Propionic Acids Transplantation, Heterologous Gazzaniga, S. Bravo, A.I. Guglielmotti, A. Van Rooijen, N. Maschi, F. Vecchi, A. Mantovani, A. Mordoh, J. Wainstok, R. Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft |
| topic_facet |
2 methyl 2 [(1 (phenylmethyl) 1h indazol 3yl)methoxy]propanoic acid clodronic acid monocyte chemotactic protein 1 propionic acid derivative unclassified drug animal cell animal experiment animal model animal tissue article cancer inhibition controlled study expression vector genetic transfection human human cell melanoma mouse nonhuman priority journal tumor associated leukocyte tumor growth tumor necrosis tumor vascularization xenograft Animals Antigens, CD31 Cell Line, Tumor Chemokine CCL2 Clodronic Acid Humans Indazoles Liposomes Macrophages Male Melanoma, Experimental Mice Neoplasm Transplantation Neovascularization, Pathologic Propionic Acids Transplantation, Heterologous |
| 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+ 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. © 2007 The Society for Investigative Dermatology. |
| format |
JOUR |
| author |
Gazzaniga, S. Bravo, A.I. Guglielmotti, A. Van Rooijen, N. Maschi, F. Vecchi, A. Mantovani, A. Mordoh, J. Wainstok, R. |
| author_facet |
Gazzaniga, S. Bravo, A.I. Guglielmotti, A. Van Rooijen, N. Maschi, F. Vecchi, A. Mantovani, A. Mordoh, J. Wainstok, R. |
| author_sort |
Gazzaniga, S. |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_0022202X_v127_n8_p2031_Gazzaniga |
| work_keys_str_mv |
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