Inhibition of carcinoma cell-derived VEGF reduces inflammatory characteristics in xenograft carcinoma

Int J Cancer. 2006 Dec 15;119(12):2795-802. doi: 10.1002/ijc.22217.


The stroma of carcinomas shares several characteristics with inflamed tissues including a distorted vasculature, active angiogenesis and macrophage infiltration. In addition, the tumor interstitial fluid pressure (P(IF)) of the stroma is pathologically elevated. We show here that bevacizumab [rhuMab vascular endothelial growth factor (VEGF), Avastin], a monoclonal antibody to VEGF, at a dose of 5 mg/kg modulated inflammation in KAT-4 xenograft human anaplastic thyroid carcinoma tissue. At this dose, bevacizumab reduced the density of macrophages, MHC class II antigen expression by macrophages and IL-1beta mRNA expression. Furthermore, bevacizumab lowered tumor extracellular fluid volume, plasma protein leakage from tumor vessels, the number of CD31-positive structures and tumor P(IF). The tumor plasma volume and the number of alpha-smooth muscle actin-positive vessels, however, remained unchanged. Our data suggest that carcinoma cell-derived VEGF either directly or indirectly participates in maintaining an inflammatory microenvironment in experimental KAT-4 carcinoma. Furthermore, our data indicate that the reduction of inflammation resulting in reduced vascular permeability and decrease in the tumor extracellular fluid volume by bevacizumab contributes to reduced tumor P(IF).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Cell Count
  • Cell Line, Tumor
  • Chemokines / genetics
  • Cytokines / genetics
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Gene Expression / drug effects
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Macrophages / drug effects
  • Macrophages / pathology
  • Mice
  • Mice, SCID
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control
  • Plasma Volume / drug effects
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / prevention & control*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology*
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Chemokines
  • Cytokines
  • Platelet Endothelial Cell Adhesion Molecule-1
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Bevacizumab