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Updated: Oct 9, 2025

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
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KLK3 in the Regulation of Angiogenesis-Tumorigenic or Not?

Hannu Koistinen1, Jaana Künnapuu2, Michael Jeltsch2,3,4

  • 1Department of Clinical Chemistry, Helsinki University Hospital and University of Helsinki, 00290 Helsinki, Finland.

International Journal of Molecular Sciences
|December 24, 2021
PubMed

Insights

Kallikrein-related peptidase 3 (KLK3), or prostate-specific antigen (PSA), has a dual role in regulating blood vessel growth. While early research indicated KLK3 inhibits angiogenesis, newer studies show it can promote it by activating VEGF-C and VEGF-D.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Kallikrein-related peptidase 3 (KLK3), commonly known as prostate-specific antigen (PSA), is a serine protease primarily associated with prostate cancer.
  • Angiogenesis, the formation of new blood vessels, is a critical process in both physiological and pathological conditions, including cancer progression.

Purpose of the Study:

  • To review the complex and often contradictory roles of KLK3/PSA in the regulation of angiogenesis.
  • To explore the mechanisms underlying KLK3's pro-angiogenic and anti-angiogenic activities.

Main Methods:

  • Literature review of existing studies on KLK3/PSA and its involvement in angiogenesis.
  • Analysis of experimental evidence detailing KLK3's proteolytic activity and its targets.
  • Examination of studies investigating KLK3's interaction with vascular endothelial growth factors (VEGFs).

Main Results:

  • Early research suggested KLK3/PSA possesses anti-angiogenic properties, likely due to its enzymatic activity.
  • More recent findings indicate KLK3/PSA can promote angiogenesis by activating VEGF-C and VEGF-D.
  • The dual role of KLK3/PSA in angiogenesis is dependent on context and specific molecular interactions.

Conclusions:

  • KLK3/PSA exhibits a dichotomous role in angiogenesis, acting as both an inhibitor and promoter.
  • Understanding the regulatory mechanisms of KLK3/PSA in angiogenesis is crucial for developing targeted therapies, particularly in prostate cancer.
Keywords:
KLK3PSAVEGF-CVEGF-Dangiogenesiscancerproteolysis

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