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 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.
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
Thorsten
T
Hagemann
Julia
J
Wilson
Frances
F
Burke
Hagen
H
Kulbe
Ninfeng Fiona
NF
Li
Annette
A
Plüddemann
Kellie
K
Charles
Siamon
S
Gordon
Frances R
FR
Balkwill
D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000503:physiopathology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics
D018925:Chemokines; D016207:Cytokines; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha