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Updated: Aug 20, 2025

Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
10:07

Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages

Published on: June 23, 2013

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KDM6B regulates M2 polarization of macrophages by modulating the stability of nuclear β-catenin

Lingfang Du1, Bo Dai2, Xuan Liu2

  • 1School of Medicine, Nankai University, Tianjin 300071, China; Clinical Medical Research Center, the Third Affiliated Hospital of Soochow University, Changzhou 213003, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|November 25, 2022
PubMed

Insights

Epigenetic regulator KDM6B prevents M2 polarization by degrading beta-catenin. Vitamin D analogs upregulate KDM6B, suppressing tumor progression and offering novel epigenetic therapy potential for cancer.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Immunology

Background:

  • Epigenetic regulation influences tumor-associated macrophage (TAM) phenotype and function.
  • KDM6B, an epigenetic enzyme, affects macrophage polarization, but its mechanism in TAMs is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which KDM6B regulates macrophage polarization in breast cancer.
  • To investigate the therapeutic potential of targeting KDM6B in a breast cancer model.

Main Methods:

  • Co-culture of breast cancer cells with TAMs to induce M2 polarization.
  • Inhibition and assessment of KDM6B activity.
  • Analysis of beta-catenin/c-Myc signaling pathway.
  • Xenograft mouse model of breast cancer treated with paricalcitol.

Main Results:

  • KDM6B inhibition increased M2 polarization in TAMs.
  • KDM6B downregulation activated beta-catenin/c-Myc signaling, promoting M2-like phenotype.
  • KDM6B's demethylase activity promoted intranuclear degradation of beta-catenin.
  • Paricalcitol (an activated vitamin D analog) upregulated KDM6B, decreased M2 polarization, and inhibited tumor growth in vivo.

Conclusions:

  • KDM6B epigenetically suppresses M2 polarization by enhancing beta-catenin degradation.
  • Activated vitamin D analogs represent a potential epigenetic therapy for cancer by modulating KDM6B and suppressing tumor progression.
Keywords:
KDM6BM2 polarizationParicalcitolTumor-associated macrophagesβ-Catenin

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