Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, SOX2, and CD44

Kirsi Kainulainen1, Einari A Niskanen1, Johanna Kinnunen1

  • 1Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.

Oncoimmunology
|August 23, 2024
PubMed

Insights

Pro-inflammatory M1 macrophages promote prostate cancer stemness and plasticity by secreting factors that upregulate cancer stem cell markers via NFκB signaling, impacting tumor progression.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • The tumor microenvironment (TME) significantly influences cancer progression.
  • Tumor-associated macrophages (TAMs) are key immune cells within the TME.
  • Increased TAM density correlates with poor prognosis in prostate cancer.

Purpose of the Study:

  • To investigate the impact of M1 and M2 macrophages on prostate cancer lineage plasticity.
  • To elucidate the molecular mechanisms by which macrophages influence prostate cancer cell behavior.

Main Methods:

  • Analysis of secreted factors from M1 and M2 macrophages.
  • Treatment of prostate cancer cells (LNCaP) with macrophage-conditioned media.
  • Assessment of gene expression for stemness markers (NANOG, KLF4, SOX2, OCT4, CD44) and androgen receptor (AR) pathway genes (PSA).
  • Inhibition of NFκB signaling using IKK16.

Main Results:

  • M1 macrophage factors upregulated stemness genes and downregulated androgen response genes in prostate cancer cells.
  • Expression of NANOG, KLF4, SOX2, OCT4, and CD44 was stimulated by M1 factors.
  • AR and PSA expression were suppressed by M1 macrophage factors.
  • NFκB inhibition downregulated NANOG, SOX2, CD44, and CSC plasticity.

Conclusions:

  • Secreted factors from M1 macrophages drive prostate cancer cell plasticity.
  • This plasticity is mediated by the upregulation of cancer stem cell markers through the NFκB signaling pathway.

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