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Pigment epithelium-derived factor stimulates tumor macrophage recruitment and is downregulated by the prostate tumor

Sofia Halin1, Stina Häggström Rudolfsson, Jennifer A Doll

  • 1Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. sofia.halin@medbio.umu.se

Neoplasia (New York, N.Y.)
|April 3, 2010
PubMed

Insights

Pigment epithelium-derived factor (PEDF) enhances antitumor immunity by increasing cytotoxic M1 macrophages and reducing tumor growth and metastasis. However, it also promotes macrophage accumulation, which may suppress PEDF and boost lymphangiogenesis, potentially aiding tumor progression.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Pigment epithelium-derived factor (PEDF) is known as an angiogenesis inhibitor.
  • The role of PEDF in the tumor microenvironment, particularly in prostate cancer, is not fully understood.
  • PEDF expression is often reduced during prostate tumor progression.

Purpose of the Study:

  • To investigate the effects of PEDF overexpression on the tumor microenvironment in prostate cancer.
  • To explore PEDF's influence on macrophage recruitment, antitumor immunity, angiogenesis, and metastasis.
  • To identify potential mechanisms, such as tumor necrosis factor alpha (TNFα), that regulate PEDF expression in the tumor microenvironment.

Main Methods:

  • Overexpression of PEDF in orthotopic MatLyLu rat prostate tumors.
  • Analysis of macrophage recruitment and M1 macrophage markers (inducible nitric oxide synthase).
  • Assessment of vascular and lymphangiogenic growth, tumor growth, and lymph node metastasis.
  • Investigation of PEDF downregulation by macrophage-derived tumor necrosis factor alpha (TNFα) in vitro and in vivo.

Main Results:

  • PEDF overexpression increased macrophage recruitment and the proportion of cytotoxic M1 macrophages, suggesting enhanced antitumor immunity.
  • PEDF reduced tumor vascularization, slowed tumor growth, and decreased lymph node metastasis.
  • Contrary to tumor vascularization, extratumoral lymphangiogenesis was increased; TNFα downregulated PEDF expression in prostate tumor cells.

Conclusions:

  • PEDF exhibits multifaceted effects in prostate tumors, inhibiting angiogenesis and metastasis while promoting macrophage accumulation.
  • Accumulating macrophages may initially inhibit tumor growth but can also suppress PEDF and promote lymphangiogenesis, potentially facilitating later tumor progression.
  • Understanding the complex interplay between PEDF, macrophages, and the tumor microenvironment is crucial for developing effective prostate cancer therapies.

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