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

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Abstract
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 (PIF) 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‐1β mRNA expression. Furthermore, bevacizumab lowered tumor extracellular fluid volume, plasma protein leakage from tumor vessels, the number of CD31‐positive structures and tumor PIF. The tumor plasma volume and the number of α‐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 PIF.

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