Regulation of inflammation- and angiogenesis-related gene expression in breast cancer cells and co-cultured macrophages.

摘要

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.