Tyrosine phosphorylation modulates the vascular responses of mesenteric arteries from human colorectal tumors

Biomed Res Int. 2013:2013:545983. doi: 10.1155/2013/545983. Epub 2013 Nov 10.

Abstract

The aim of this study was to analyze whether tyrosine phosphorylation in tumoral arteries may modulate their vascular response. To do this, mesenteric arteries supplying blood flow to colorectal tumors or to normal intestine were obtained during surgery and prepared for isometric tension recording in an organ bath. Increasing tyrosine phosphorylation with the phosphatase inhibitor, sodium orthovanadate produced arterial contraction which was lower in tumoral than in control arteries, whereas it reduced the contraction to noradrenaline in tumoral but not in control arteries and reduced the relaxation to bradykinin in control but not in tumoral arteries. Protein expression of VEGF-A and of the VEGF receptor FLT1 was similar in control and tumoral arteries, but expression of the VEGF receptor KDR was increased in tumoral compared with control arteries. This suggests that tyrosine phosphorylation may produce inhibition of the contraction in tumoral mesenteric arteries, which may increase blood flow to the tumor when tyrosine phosphorylation is increased by stimulation of VEGF receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Organ Culture Techniques
  • Phosphorylation / drug effects*
  • Tyrosine / metabolism
  • Vanadates / administration & dosage*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vanadates
  • Tyrosine
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1