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

Anticancer Res. 2008 Jul-Aug;28(4B):2093-9.

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

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / immunology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aspirin / pharmacology
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Cell Line, Tumor
  • Coculture Techniques
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / genetics
  • Macrophage Migration-Inhibitory Factors / biosynthesis
  • Macrophage Migration-Inhibitory Factors / genetics*
  • Macrophage Migration-Inhibitory Factors / pharmacology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / physiology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • PTEN Phosphohydrolase / biosynthesis
  • PTEN Phosphohydrolase / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tamoxifen / pharmacology
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Macrophage Migration-Inhibitory Factors
  • RNA, Neoplasm
  • Recombinant Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tamoxifen
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Aspirin