Regulation of inflammation- and angiogenesis-related gene expression in breast cancer cells and co-cultured macrophages
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-1O expression in the macrophages, MCF-7 and tamoxifen-pretreated MCF-7 cells. Aspirin-pretreated macrophages potently induced IL-1O expression in the MCF-7 cells. Conclusion: Because MIF is a determinant of the MI 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.
Burnett, Giselle T.; Weathersby, Demse C.; Taylor, Tiffany E.; and Bremner, Theodore A., "Regulation of inflammation- and angiogenesis-related gene expression in breast cancer cells and co-cultured macrophages" (2008). Howard University Cancer Center Faculty Publications. 86.