Title: Genetic Deficiency in Plasma Protein HRG Enhances Tumor Growth and Metastasis by Exacerbating Immune Escape and Vessel Abnormalization
Authors: Tugues, Sònia ×
Honjo, Satoshi
König, Christian
Noguer, Oriol
Hedlund, Marie
Botling, Johan
Deschoemaeker, Sofie
Wenes, Mathias
Rolny, Charlotte
Jahnen-Dechent, Wilhelm
Mazzone, Max
Claesson-Welsh, Lena #
Issue Date: Apr-2012
Publisher: Waverly Press
Series Title: Cancer Research vol:72 issue:8 pages:1953-1963
Abstract: Histidine-rich glycoprotein (HRG) is a 75-kDa heparin-binding plasma protein implicated in the regulation of tumor growth and vascularization. In this study, we show that hrg(-/-) mice challenged with fibrosarcoma or pancreatic carcinoma grow larger tumors with increased metastatic properties. Compared with wild-type mice, fibrosarcomas in hrg(-/-) mice were more hypoxic, necrotic, and less perfused, indicating enhanced vessel abnormalization. HRG deficiency was associated with a suppressed antitumor immune response, with both increased infiltration of M2 marker-expressing macrophages and decreased infiltration of dendritic cells and cytotoxic T cells. Analysis of transcript expression in tumor-associated as well as peritoneal macrophages from hrg(-/-) mice revealed an increased expression of genes associated with a proangiogenic and immunoinhibitory phenotype. In accordance, expression arrays conducted on HRG-treated peritoneal macrophages showed induction of genes involved in extracellular matrix biology and immune responsiveness. In conclusion, our findings show that macrophages are a direct target of HRG. HRG loss influences macrophage gene regulation, leading to excessive stimulation of tumor angiogenesis, suppression of tumor immune response, and increased tumor growth and metastatic spread.
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Tumor Inflammation and Angiogenesis (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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