Mast Cell Proteases 6 and 7 Stimulate Angiogenesis by Inducing Endothelial Cells to Release Angiogenic Factors

PLoS One. 2015 Dec 3;10(12):e0144081. doi: 10.1371/journal.pone.0144081. eCollection 2015.

Abstract

Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology
  • Angiogenic Proteins / metabolism*
  • Animals
  • Cell Line
  • Cells, Cultured
  • Chick Embryo
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Male
  • Mast Cells / cytology
  • Mast Cells / drug effects
  • Mast Cells / metabolism
  • Mice
  • Neovascularization, Pathologic / metabolism*
  • Tryptases / pharmacology*

Substances

  • Angiogenesis Inducing Agents
  • Angiogenic Proteins
  • Tpsb2 protein, mouse
  • Tpsab1 protein, mouse
  • Tryptases

Grants and funding

Funding was provided by FAPESP (Fundacão de Amparo e Pesquisa do Estado de São Paulo, http://www.fapesp.br/); Post Doctoral Fellowship 11/10363-8 to DASJ and Equipment Grant 09/54013-0 to MCJ; CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, http://www.cnpq.br) Fellowship to MCJ and ACB Post Doctoral Fellowship 150022/2012-3, FAEPA (Fundacão de Apoio ao Ensino, Pesquisa e Assistência, http://www.faepa.br) Grant to MCJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.