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

PLoS One. 2013 Jul 9;8(7):e68033. doi: 10.1371/journal.pone.0068033. Print 2013.

Abstract

Protein kinase D isoenzymes (PKDs, Prkds) are serine threonine kinases that belong to the CAMK superfamily. PKD1 is expressed in endothelial cells and is a major mediator of biological responses downstream of the VEGFRs that are relevant for angiogenesis such as endothelial cell migration, proliferation and tubulogenesis in vitro. PKDs also play a critical role in tumor development and progression, including tumor angiogenesis. However, given the plethora of signaling modules that drive angiogenesis, the precise role of PKD1 in both physiological and tumor angiogenesis in vivo has not been worked out so far. This study aimed at dissecting the contribution of PKD1 to physiological blood vessel formation, PKD1 was found to be widely expressed during zebrafish development. As far as physiological angiogenesis was concerned, morpholino-based silencing of PKD1 expression moderately reduced the formation of the intersomitic vessels and the dorsal longitudinal anastomotic vessel in tg(fli1:EGFP) zebrafish. In addition, silencing of PKD1 resulted in reduced formation of the parachordal lymphangioblasts that serves as a precursor for the developing thoracic duct. Interestingly, tumor angiogenesis was completely abolished in PKD1 morphants using the zebrafish/tumor xenograft angiogenesis assay. Our data in zebrafish demonstrate that PKD1 contributes to the regulation of physiological angiogenesis and lymphangiogenesis during zebrafish development and is essential for tumor angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Silencing
  • Humans
  • Lymphangiogenesis / genetics
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Physiologic / genetics*
  • Protein Kinase C / genetics*
  • Protein Kinase C / metabolism
  • Zebrafish / genetics*
  • Zebrafish / metabolism

Substances

  • protein kinase D
  • Protein Kinase C

Grants and funding

This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB/TR23, project Z5 to J.K. and INST 91027/10-1 FUGG) by the German Federal Ministry of Education and Research (BMBF) grant no. NGFN plus/PKB-01GS08209-4 (to T.S.), and the Deutsche Krebshilfe to T.S., by the Wilhelm-Roux-program from the Martin-Luther-University Halle (Saale) (to M.H.) and by the German Cardiac Society (to S.J.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.