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Genetic deficiency ...
Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization
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- Tugues, Sònia (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Honjo, Satoshi (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- König, Christian (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Noguer, Oriol (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Hedlund, Marie (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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- Botling, Johan (author)
- Uppsala universitet,Molekylär och morfologisk patologi
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Deschoemaeker, Sofie (author)
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Wenes, Mathias (author)
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- Rolny, Charlotte (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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Jahnen-Dechent, Wilhelm (author)
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Mazzone, Massimiliano (author)
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- Claesson-Welsh, Lena (author)
- Uppsala universitet,Cancer och vaskulärbiologi
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(creator_code:org_t)
- 2012
- 2012
- English.
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In: Cancer Research. - 0008-5472 .- 1538-7445.
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- Pathology
- Patologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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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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Jahnen-Dechent, ...
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Mazzone, Massimi ...
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Claesson-Welsh, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
- Articles in the publication
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Cancer Research
- By the university
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Uppsala University