Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype |
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Authors: | Hagemann Thorsten Wilson Julia Burke Frances Kulbe Hagen Li Ninfeng Fiona Plüddemann Annette Charles Kellie Gordon Siamon Balkwill Frances R |
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Affiliation: | Cancer Research United Kingdom Translational Oncology Laboratory, Barts & The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, United Kingdom. t.hagemann@qmul.ac.uk |
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Abstract: | 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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