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Different regulation of physiological and tumor angiogenesis in zebrafish by protein kinase D1 (PKD1)

Marcus Hollenbach1, Sandra Jasmin Stoll, Kristina Jörgens

  • 1Department of Vascular Biology & Tumorangiogenesis, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.

Plos One
|July 23, 2013
PubMed

Insights

Protein kinase D1 (PKD1) supports physiological blood vessel formation and lymphangiogenesis in zebrafish. However, PKD1 is essential for tumor angiogenesis, highlighting its critical role in cancer progression.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Protein kinase D isoenzymes (PKDs) are serine/threonine kinases involved in cellular signaling.
  • PKD1 mediates VEGFR-dependent endothelial cell responses crucial for angiogenesis.
  • PKDs are implicated in tumor development and angiogenesis, but their in vivo roles remain unclear.

Purpose of the Study:

  • To investigate the role of Protein kinase D1 (PKD1) in physiological and tumor angiogenesis in vivo.
  • To dissect the contribution of PKD1 to blood vessel and lymphatic vessel formation during zebrafish development.

Main Methods:

  • Utilized zebrafish as a model organism for in vivo studies.
  • Employed morpholino-based gene silencing to inhibit PKD1 expression.
  • Assessed physiological angiogenesis by examining intersomitic vessels and dorsal longitudinal anastomotic vessel formation.
  • Evaluated lymphangiogenesis by observing parachordal lymphangioblast development.
  • Investigated tumor angiogenesis using a zebrafish/tumor xenograft model.

Main Results:

  • PKD1 is widely expressed during zebrafish development.
  • PKD1 inhibition moderately reduced physiological angiogenesis (inter-somitic vessels, dorsal longitudinal anastomotic vessel).
  • PKD1 silencing impaired lymphangiogenesis, affecting parachordal lymphangioblast formation.
  • Tumor angiogenesis was completely abolished in PKD1-deficient zebrafish.

Conclusions:

  • PKD1 plays a role in regulating physiological angiogenesis and lymphangiogenesis during zebrafish development.
  • PKD1 is essential for tumor angiogenesis in vivo.
  • Targeting PKD1 may represent a therapeutic strategy for inhibiting tumor growth.

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