Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.

Tumor-associated macrophages (TAM) may have tumor-promoting activity, but it is not clear how their phenotype is achieved. In this study, we demonstrate that ovarian cancer cells switch cocultured macrophages to a phenotype similar to that found in ovarian tumors. Tumor cells caused dynamic changes...

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Main Authors: Hagemann, T, Wilson, J, Burke, F, Kulbe, H, Li, N, Plüddemann, A, Charles, K, Gordon, S, Balkwill, F
Format: Journal article
Language:English
Published: 2006
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author Hagemann, T
Wilson, J
Burke, F
Kulbe, H
Li, N
Plüddemann, A
Charles, K
Gordon, S
Balkwill, F
author_facet Hagemann, T
Wilson, J
Burke, F
Kulbe, H
Li, N
Plüddemann, A
Charles, K
Gordon, S
Balkwill, F
author_sort Hagemann, T
collection OXFORD
description Tumor-associated macrophages (TAM) may have tumor-promoting activity, but it is not clear how their phenotype is achieved. In this study, we demonstrate that ovarian cancer cells switch cocultured macrophages to a phenotype similar to that found in ovarian tumors. Tumor cells caused dynamic changes in macrophage cytokine, chemokine, and matrix metalloprotease mRNA, and protein-inducing mediators that are found in human cancer. Macrophage mannose, mannose receptor, and scavenger receptors (SR-As) were also up-regulated by coculture, but not by conditioned medium. To further validate the model, we studied SR-A regulation on TAM in vitro and in vivo. Coculture of murine macrophages from mice deficient in TNF-alpha or its receptors revealed that TNF-alpha was key to SR-A induction via its p75 receptor. SR-A expression was also reduced in TAM from ovarian cancers treated with anti-TNF-alpha Abs or grown in TNF-alpha(-/-) mice. Chemical communication between tumor cells and macrophages may be important in regulating the cancer cytokine microenvironment.
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spelling oxford-uuid:577f2130-11cc-4ad9-94e8-653b6508b7c42022-03-26T16:57:08ZOvarian cancer cells polarize macrophages toward a tumor-associated phenotype.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:577f2130-11cc-4ad9-94e8-653b6508b7c4EnglishSymplectic Elements at Oxford2006Hagemann, TWilson, JBurke, FKulbe, HLi, NPlüddemann, ACharles, KGordon, SBalkwill, FTumor-associated macrophages (TAM) may have tumor-promoting activity, but it is not clear how their phenotype is achieved. In this study, we demonstrate that ovarian cancer cells switch cocultured macrophages to a phenotype similar to that found in ovarian tumors. Tumor cells caused dynamic changes in macrophage cytokine, chemokine, and matrix metalloprotease mRNA, and protein-inducing mediators that are found in human cancer. Macrophage mannose, mannose receptor, and scavenger receptors (SR-As) were also up-regulated by coculture, but not by conditioned medium. To further validate the model, we studied SR-A regulation on TAM in vitro and in vivo. Coculture of murine macrophages from mice deficient in TNF-alpha or its receptors revealed that TNF-alpha was key to SR-A induction via its p75 receptor. SR-A expression was also reduced in TAM from ovarian cancers treated with anti-TNF-alpha Abs or grown in TNF-alpha(-/-) mice. Chemical communication between tumor cells and macrophages may be important in regulating the cancer cytokine microenvironment.
spellingShingle Hagemann, T
Wilson, J
Burke, F
Kulbe, H
Li, N
Plüddemann, A
Charles, K
Gordon, S
Balkwill, F
Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
title Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
title_full Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
title_fullStr Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
title_full_unstemmed Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
title_short Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype.
title_sort ovarian cancer cells polarize macrophages toward a tumor associated phenotype
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