Reciprocal activation of macrophages and breast carcinoma cells by nitric oxide and colony-stimulating factor-1

Cheng Wei Liny, Shing-Chuan Shen, Ching Huai Ko, Hui Yi Lin, Yen-Chou Chen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Induction of inducible nitric oxide synthase (iNOS) gene expression, nitric oxide (NO) production and migration of RAW264.7 macrophages by coculture with breast cancer MDA-MB-231 cells or the addition of conditioned medium derived from MDA-MB-231 cells (MDA-CM) was identified. Increased iNOS/NO induction and migration of macrophages byMDA-CM were significantly blocked by adding the c-Jun-N-terminal protein kinase (JNK) inhibitor, SP600125, the nuclear factor-kappa B (NF-κB) inhibitor, BAY117082 and pyrrolidine dithiocarbamic acid and a dominant-negative JNK. The addition of an NO donor, Diethylenetriamine-NONOate, significantly activated expressions of MMP-9 and VEGF-A genes in breast carcinoma MDA-MD-231 cells and invasion of MDA-MB-231 cells in coculture with RAW264.7 macrophages as determined using Transwell systems, but that was inhibited by adding SP600125, BAY117082 and the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester. Induction of heme oxygenase-1 in macrophages reduced MDACM-induced iNOS/NO, JNK and NF-κB activations in accordance with inhibiting VEGF-A and MMP-9 gene expressions by MDA-MB-231 cells via Transwell assays. Furthermore, VEGF, sRANKL, TNF-α, IL-1α, TGF-β, CSF-1 andMCP-1 were applied, and CSF-1 showed the most potent stimulation of iNOS/NO production and migration of macrophages. MCF-7 cells with lower CSF-1 expression than MDA-MB-231 cells showed a poor stimulatory effect on iNOS/NO production and migration of macrophages. Neutralization of CSF-1 in MDA-CM using CSF-1 antibody inhibited MDA-CM-induced iNOS protein expression and migration of macrophages, and CSF-1-induced iNOS protein and migration was blocked by adding JNK inhibitor SP and NF-κB inhibitor BAY. The reciprocal activation of breast cancer and macrophages via NO-CSF-1 is first elucidated herein.

Original languageEnglish
Pages (from-to)2039-2048
Number of pages10
JournalCarcinogenesis
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 2010

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Macrophage Colony-Stimulating Factor
Macrophage Activation
Nitric Oxide Synthase Type II
Nitric Oxide
Macrophages
Breast Neoplasms
Vascular Endothelial Growth Factor A
NF-kappa B
Protein Kinase Inhibitors
Coculture Techniques
Matrix Metalloproteinases
vif Genes
Gene Expression
Proteins
Heme Oxygenase-1
Nitric Oxide Donors
JNK Mitogen-Activated Protein Kinases
NG-Nitroarginine Methyl Ester
MCF-7 Cells
Conditioned Culture Medium

ASJC Scopus subject areas

  • Cancer Research

Cite this

Reciprocal activation of macrophages and breast carcinoma cells by nitric oxide and colony-stimulating factor-1. / Liny, Cheng Wei; Shen, Shing-Chuan; Ko, Ching Huai; Lin, Hui Yi; Chen, Yen-Chou.

In: Carcinogenesis, Vol. 31, No. 12, 12.2010, p. 2039-2048.

Research output: Contribution to journalArticle

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