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

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.

• Authors: Thorsten Hagemann, Julia Wilson, Frances Burke, Hagen Kulbe, Ninfeng Fiona Li, Annette Plüddemann, Kellie Charles, Siamon Gordon, Frances R Balkwill
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 8 Pg. 5023-32 (Apr 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16585599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokines
• Cytokines
• Lectins, C-Type
• Mannose Receptor
• Mannose-Binding Lectins
• Receptors, Cell Surface
• Scavenger Receptors, Class A
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Cell Communication
• Cell Line, Tumor
• Chemokines (biosynthesis, genetics)
• Coculture Techniques
• Cytokines (biosynthesis, genetics)
• Female
• Gene Expression
• Humans
• Lectins, C-Type (metabolism)
• Macrophage Activation
• Macrophages (immunology, physiology)
• Mannose Receptor
• Mannose-Binding Lectins (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovarian Neoplasms (immunology, physiopathology)
• Phenotype
• Receptors, Cell Surface (metabolism)
• Scavenger Receptors, Class A (metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, deficiency, genetics)