Abstract
Background:
Tumor-associated macrophages (TAMs) secrete key modifiers of tumor progression and their modification has been proposed as a therapeutic strategy. Phenotypic changes that may render TAMs selectively vulnerable to anti-cancer agents were examined.
Materials and methods:
Gene arrays, reverse transcription-polymerase chain reaction and Western blotting were used to study inflammation- and angiogenesis-related gene expression in co-cultured breast cancer cells and macrophages and to determine how their interactions were affected by tamoxifen and aspirin.
Results:
MCF-7 (mammary adenocarcinoma) cells down-regulated macrophage migration inhibitory factor (MIF), but tamoxifen-pretreated MCF-7 cells up-regulated MIF in co-cultured macrophages. Two molecular variants of MIF were observed in the co-cultured MCF-7 cells. Aspirin induced IL-10 expression in the macrophages, MCF-7 and tamoxifen-pretreated MCF-7 cells. Aspirin-pretreated macrophages potently induced IL-10 expression in the MCF-7 cells.
Conclusion:
Because MIF is a determinant of the M1 macrophage activation state, the MCF-7-induced ablation of MIF in TAMs is suggestive of partial M2 polarization. Tamoxifen modulates MCF-7 regulation of TAM gene expression and aspirin alters macrophage regulation of MCF-7 gene expression.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma / blood supply
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Adenocarcinoma / genetics*
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Adenocarcinoma / immunology
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Aspirin / pharmacology
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Breast Neoplasms / blood supply
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Breast Neoplasms / genetics*
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Breast Neoplasms / immunology
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Cell Line, Tumor
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Coculture Techniques
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Down-Regulation / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology*
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Humans
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Inflammation / genetics
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Inflammation / immunology
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / genetics
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Macrophage Migration-Inhibitory Factors / biosynthesis
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Macrophage Migration-Inhibitory Factors / genetics*
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Macrophage Migration-Inhibitory Factors / pharmacology
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Macrophages / drug effects
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Macrophages / immunology
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Macrophages / physiology*
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / immunology
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Neovascularization, Pathologic / pathology
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PTEN Phosphohydrolase / biosynthesis
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PTEN Phosphohydrolase / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Tamoxifen / pharmacology
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Interleukin-1beta
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Macrophage Migration-Inhibitory Factors
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RNA, Neoplasm
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Recombinant Proteins
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TP53 protein, human
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Tumor Suppressor Protein p53
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Tamoxifen
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PTEN Phosphohydrolase
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PTEN protein, human
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Aspirin