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Updated: Sep 26, 2025

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Macrophages Cytokine Spp1 Increases Growth of Prostate Intraepithelial Neoplasia to Promote Prostate Tumor

Justin K Messex1, Crystal J Byrd2, Mikalah U Thomas2

  • 1Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA 30314, USA.

International Journal of Molecular Sciences
|April 23, 2022
PubMed

Insights

Macrophages promote prostate cancer progression by secreting osteopontin (Spp1). This Spp1 activates pathways in prostatic intraepithelial neoplasia (PIN) cells, accelerating their growth and leading to cancer development.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Prostate cancer progression correlates with increased macrophage infiltration.
  • The role of macrophages in the progression of prostatic intraepithelial neoplasia (PIN) to prostate cancer is not fully understood.

Purpose of the Study:

  • To investigate the role of macrophages in PIN progression.
  • To identify the mechanisms by which macrophages influence PIN cell growth.

Main Methods:

  • Analysis of macrophage markers and Spp1 (osteopontin) expression in PIN lesions.
  • 3D cell culture experiments to assess the effect of Spp1 on PIN cell proliferation.
  • Investigation of Spp1 receptor expression (CD44, integrins) on PIN cells.
  • Inhibition of Akt and JNK signaling pathways to block Spp1-mediated proliferation.

Main Results:

  • Macrophages adjacent to PIN lesions exhibited M2 markers and high Spp1 levels.
  • Exogenous Spp1 significantly increased PIN cell proliferation via Akt and JNK activation.
  • PIN cells expressed known Spp1 receptors (CD44, integrin αv, β1, β3).
  • Inhibiting Akt and JNK abolished Spp1-induced PIN cell proliferation.

Conclusions:

  • Macrophage-derived Spp1 acts as a cytokine/growth factor that promotes prostate cancer development.
  • Spp1 upregulates PIN cell growth by activating Akt and JNK signaling pathways.
  • Targeting the Spp1-mediated pathway could offer a therapeutic strategy for prostate cancer.
Keywords:
3D cultureCD44Spp1integrinmacrophageosteopontinprostate intraepithelial neoplasiaprostate tumor growth

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