Cancer Cell Biology
Inhibition of carcinoma cell-derived VEGF reduces inflammatory characteristics in xenograft carcinoma
Alexei V. Salnikov,
Nils-Erik Heldin,
Linda B. Stuhr,
Helge Wiig,
Hanspeter Gerber,
Rolf K. Reed,
Kristofer Rubin,
Alexei V. Salnikov
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Department of Oncology, Clinical Sciences Lund, Lund University, Lund, Sweden
Search for more papers by this authorNils-Erik Heldin
Department of Genetics and Pathology, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden
Search for more papers by this authorLinda B. Stuhr
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorHelge Wiig
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorHanspeter Gerber
Department of Molecular Oncology, Genentech, South San Francisco, CA
Search for more papers by this authorRolf K. Reed
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorCorresponding Author
Kristofer Rubin
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Fax: +46-18-471-4975
Department of Medical Biochemistry and Microbiology, University of Uppsala, BMC, Box 582, SE-751 23 Uppsala, SwedenSearch for more papers by this authorAlexei V. Salnikov,
Nils-Erik Heldin,
Linda B. Stuhr,
Helge Wiig,
Hanspeter Gerber,
Rolf K. Reed,
Kristofer Rubin,
Alexei V. Salnikov
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Department of Oncology, Clinical Sciences Lund, Lund University, Lund, Sweden
Search for more papers by this authorNils-Erik Heldin
Department of Genetics and Pathology, Uppsala University Hospital, Rudbeck Laboratory, Uppsala, Sweden
Search for more papers by this authorLinda B. Stuhr
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorHelge Wiig
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorHanspeter Gerber
Department of Molecular Oncology, Genentech, South San Francisco, CA
Search for more papers by this authorRolf K. Reed
Department of Biomedicine, University of Bergen, Bergen, Norway
Search for more papers by this authorCorresponding Author
Kristofer Rubin
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
Fax: +46-18-471-4975
Department of Medical Biochemistry and Microbiology, University of Uppsala, BMC, Box 582, SE-751 23 Uppsala, SwedenSearch for more papers by this authorAbstract
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. © 2006 Wiley-Liss, Inc.
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