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Genetic deficiency ...
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Tugues, SòniaUppsala universitet,Cancer och vaskulärbiologi
(author)
Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization
- Article/chapterEnglish2012
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LIBRIS-ID:oai:DiVA.org:uu-170988
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-170988URI
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https://doi.org/10.1158/0008-5472.CAN-11-2194DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 carcinomas 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 anti-tumor 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 pro-angiogenic and immunoinhibitory phenotype. In accordance, expression arrays performed on HRG-treated peritoneal macrophages showed induction of genes involved in extracellular matrix biology and immune responsiveness. In conclusion, our findings demonstrate that macrophages are a direct target of HRG. HRG loss influences macrophage gene regulation, leading to excess stimulation of tumor angiogenesis, suppression of tumor immune response, and increased tumor growth and metastatic spread.
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Honjo, SatoshiUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)satho511
(author)
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König, ChristianUppsala universitet,Institutionen för immunologi, genetik och patologi
(author)
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Noguer, OriolUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)orino300
(author)
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Hedlund, MarieUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)mimmjoha
(author)
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Botling, JohanUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)johanbot
(author)
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Deschoemaeker, Sofie
(author)
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Wenes, Mathias
(author)
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Rolny, CharlotteUppsala universitet,Cancer och vaskulärbiologi
(author)
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Jahnen-Dechent, Wilhelm
(author)
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Mazzone, Massimiliano
(author)
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Claesson-Welsh, LenaUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)lcl04207
(author)
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Uppsala universitetCancer och vaskulärbiologi
(creator_code:org_t)
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In:Cancer Research0008-54721538-7445
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Tugues, Sònia
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Honjo, Satoshi
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König, Christian
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Noguer, Oriol
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Hedlund, Marie
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Botling, Johan
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Deschoemaeker, S ...
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Wenes, Mathias
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Rolny, Charlotte
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