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Updated: Jun 15, 2025

In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells
Published on: February 18, 2015
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.
Abstract:
The inflammatory tumor microenvironment (TME) is a key driver for tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their increased density is related to poor prognosis in prostate cancer. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in prostate cancer cells. The expression of cancer stem cell (CSC) plasticity markers NANOG, KLF4, SOX2, OCT4, and CD44 was stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene PSA were observed to be suppressed in LNCaP cells treated with secreted factors from M1 macrophages. Inhibition of NFκB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, SOX2, and CD44 and CSC plasticity. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of CSC plasticity markers through NFκB signaling pathway.
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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