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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

Publisher, publication year, extent ...

  • 2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-170988
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-170988URI
  • https://doi.org/10.1158/0008-5472.CAN-11-2194DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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)
  • König, ChristianUppsala universitet,Institutionen för immunologi, genetik och patologi (author)
  • Noguer, OriolUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)orino300 (author)
  • Hedlund, MarieUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)mimmjoha (author)
  • Botling, JohanUppsala universitet,Molekylär och morfologisk patologi(Swepub:uu)johanbot (author)
  • Deschoemaeker, Sofie (author)
  • Wenes, Mathias (author)
  • Rolny, CharlotteUppsala universitet,Cancer och vaskulärbiologi (author)
  • Jahnen-Dechent, Wilhelm (author)
  • Mazzone, Massimiliano (author)
  • Claesson-Welsh, LenaUppsala universitet,Cancer och vaskulärbiologi(Swepub:uu)lcl04207 (author)
  • Uppsala universitetCancer och vaskulärbiologi (creator_code:org_t)

Related titles

  • In:Cancer Research0008-54721538-7445

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