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Published on: November 28, 2019
Positive correlation between PEDF expression levels and macrophage density in the human prostate
Thomas Nelius1, Christina Samathanam, Dalia Martinez-Marin
1Department of Urology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6591, USA.
Background:
In this study, we investigated the capacity of pigment epithelium-derived factor (PEDF) to modulate the recruitment and the differentiation of monocytes/macrophages both in vitro and in human prostate.
Methods:
Using Boyden chambers, we assessed PEDF effect on the migration of monocytes and chemically activated RAW 264.7 macrophages. Normal, prostatitis, and prostate cancer specimens were retrospectively selected and examined by immunohistochemistry for PEDF expression and infiltration of immune CD68 + macrophagic cells. PEDF expression and macrophage density were then correlated with each other and clinicopathological parameters. M1 and M2 differentiation markers were quantified by qRT-PCR, Western blotting, and ELISA.
Results:
In chemotaxis, PEDF induced the migration of monocytes/macrophages. In immunohistochemistry, macrophages were markedly increased in prostatitis and malignant compared to normal tissues. PEDF was expressed at variable levels in the stroma and epithelium. PEDF mRNA was down-regulated in both prostate cancer and prostatitis compared to normal tissues. In correlation studies, macrophage density and PEDF expression were respectively positively and negatively associated with prostate size. Most importantly, PEDF expression positively correlated with macrophage density. Finally, PEDF stimulated the expression of iNOS, IL12, and TNFα; and inhibited IL10 and arginase 1 in mouse and human macrophages confirming a M1-type differentiation.
Conclusions:
Our data demonstrate that PEDF acts directly on monocytes/macrophages by inducing their migration and differentiation into M1-type cells. These findings suggest a possible role of macrophages in PEDF anti-tumor properties and may support further development of PEDF-based anti-cancer therapy.
Insights
Pigment epithelium-derived factor (PEDF) promotes monocyte/macrophage migration and M1-type differentiation, suggesting a role in anti-tumor immunity and potential for cancer therapy.
Area of Science:
- Immunology
- Cancer Biology
- Prostate Research
Background:
- Investigating the role of pigment epithelium-derived factor (PEDF) in modulating immune cell behavior within the prostate.
- Understanding the interplay between PEDF, monocytes, and macrophages in both healthy and diseased prostate tissues.
Purpose of the Study:
- To determine PEDF's capacity to influence monocyte/macrophage recruitment and differentiation.
- To explore the correlation between PEDF expression, macrophage infiltration, and clinicopathological parameters in human prostate samples.
Main Methods:
- Utilized Boyden chambers to assess PEDF's effect on monocyte and macrophage migration.
- Conducted immunohistochemistry on human prostate tissues (normal, prostatitis, prostate cancer) to evaluate PEDF expression and CD68+ macrophage infiltration.
- Quantified M1 and M2 macrophage differentiation markers using qRT-PCR, Western blotting, and ELISA.
Main Results:
- PEDF significantly induced monocyte/macrophage migration in vitro.
- Macrophage infiltration was elevated in prostatitis and prostate cancer tissues compared to normal tissues.
- PEDF expression correlated positively with macrophage density and was associated with M1-type differentiation, characterized by increased iNOS, IL12, TNFα, and decreased IL10, arginase 1.
Conclusions:
- PEDF directly promotes monocyte/macrophage migration and M1 differentiation.
- Macrophages may contribute to PEDF's anti-tumor effects.
- These findings support the potential development of PEDF-based anti-cancer therapies.
