Macrophages induce COX-2 expression in breast cancer cells: role of IL-1ß autoamplification.
Carcinogenesis
; 32(5): 695-702, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21310944
ABSTRACT
Tumor-associated macrophages and high levels of cyclooxygenase-2 (COX-2) are associated with poor prognosis in breast cancer patients, but their potential interdependence has not been evaluated. The objective of this study was to determine whether macrophages regulate COX-2 expression in breast cancer cells. For this purpose, THP-1 cells were cocultured with HCC1954 breast cancer cells. Coculture led to increased COX-2 expression in the HCC1954 cells and elevated prostaglandin E(2) levels in conditioned media. Similar results were observed when THP-1 cells were incubated with HCC1937 breast cancer cells or when human monocyte-derived macrophages were cocultured with HCC1954 cells. Coculture triggered production of reactive oxygen species (ROS) in HCC1954 cells. COX-2 induction was blocked in cells preincubated with an reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or by silencing p67PHOX, a subunit of NADPH oxidase. ROS production triggered activation of Src and mitogen-activated protein kinases (MAPKs). Blocking Src or MAPK activities or antagonizing the activator protein-1 (AP-1) transcription factor attenuated COX-2 induction in HCC1954 cells. Coculture caused rapid induction of interleukin-1ß (IL-1ß) in both breast cancer cells and macrophages. Increased IL-1ß expression was blocked by an interleukin-1 receptor antagonist (IL-1Ra), suggesting autocrine and paracrine effects. Importantly, macrophage-induced COX-2 expression was blocked in HCC1954 cells preincubated with IL-1Ra or anti-IL-1ß IgG. Together, these results indicate that macrophage-mediated induction of COX-2 in breast cancer cells is a consequence of IL-1ß-mediated stimulation of ROSâSrcâMAPKâAP-1 signaling. IL-1ß-dependent induction of COX-2 in breast cancer cells provides a mechanism whereby macrophages contribute to tumor progression and potential therapeutic targets in breast cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Amplificação de Genes
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Macrófagos Peritoneais
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Ciclo-Oxigenase 2
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Interleucina-1beta
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos