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Updated: May 7, 2026

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
09:03

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Published on: November 23, 2014

Distinct roles of DKK1 and DKK2 in tumor angiogenesis

Hongryeol Park1, Hyei Yoon Jung, Hyun-Jung Choi

  • 1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752, Republic of Korea.

Angiogenesis
|October 5, 2013
PubMed

Insights

Dickkopf-1 (DKK1) inhibits tumor growth and vascularization, while its homolog Dickkopf-2 (DKK2) promotes them. These findings reveal their distinct roles in regulating tumor blood vessel normalization and functionality.

Area of Science:

  • Oncology
  • Vascular Biology
  • Molecular Biology

Background:

  • Tumor angiogenesis is crucial for cancer growth and metastasis, often resulting in abnormal vasculature.
  • Vessel normalization strategies aim to improve cancer therapy by addressing vascular abnormalities like leakage and poor pericyte coverage.
  • Dickkopf-1 (DKK1) inhibits normal tissue angiogenesis, while Dickkopf-2 (DKK2) enhances it.

Purpose of the Study:

  • To investigate the differential effects of DKK1 and DKK2 on tumor growth and angiogenesis.
  • To evaluate the impact of DKK1 and DKK2 on tumor vascular density, perfusion, and pericyte coverage.
  • To assess the roles of DKK1 and DKK2 in a model of oxygen-induced retinopathy.

Main Methods:

  • Treatment of B16F10 melanoma-bearing mice with DKK1 or DKK2 using adenovirus vectors.
  • Analysis of tumor growth, vascular density, perfusion, and pericyte coverage in treated mice.
  • Generation and analysis of endothelial-specific DKK1 and DKK2 transgenic mice.
  • Assessment of DKK1 and DKK2 effects in a murine oxygen-induced retinopathy model.

Main Results:

  • DKK1 significantly reduced tumor growth, vascular density, and perfusion, while DKK2 increased them.
  • DKK1 decreased pericyte coverage of tumor blood vessels, whereas DKK2 enhanced it.
  • DKK1 diminished retinal neovascularization, while DKK2 promoted it in an oxygen-induced retinopathy model.

Conclusions:

  • DKK1 and DKK2 exhibit opposing effects on tumor growth and angiogenesis.
  • These Dickkopf proteins play distinct roles in regulating tumor blood vessel normalization and functionality.
  • DKK1 and DKK2 represent potential therapeutic targets for modulating tumor vascularization.

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