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Sebastian Kalamajski

Assistant researcher

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Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma.

Author

  • Åke Oldberg
  • Sebastian Kalamajski
  • Alexei Salnikov
  • Linda Stuhr
  • Matthias Mörgelin
  • Rolf Reed
  • Nils-Erik Heldin
  • Kristofer Rubin

Summary, in English

Research on the biology of the tumor stroma has the potential to lead to development of more effective treatment regimes enhancing the efficacy of drug-based treatment of solid malignancies. Tumor stroma is characterized by distorted blood vessels and activated connective tissue cells producing a collagen-rich matrix, which is accompanied by elevated interstitial fluid pressure (IFP), indicating a transport barrier between tumor tissue and blood. Here, we show that the collagen-binding proteoglycan fibromodulin controls stroma structure and fluid balance in experimental carcinoma. Gene ablation or inhibition of expression by anti-inflammatory agents showed that fibromodulin promoted the formation of a dense stroma and an elevated IFP. Fibromodulin-deficiency did not affect vasculature but increased the extracellular fluid volume and lowered IFP. Our data suggest that fibromodulin controls stroma matrix structure that in turn modulates fluid convection inside and out of the stroma. This finding is particularly important in relation to the demonstration that targeted modulations of the fluid balance in carcinoma can increase the response to cancer therapeutic agents.

Department/s

  • Åke Oldberg´s group
  • Rheumatology
  • Breastcancer-genetics
  • Infection Medicine (BMC)

Publishing year

2007

Language

English

Pages

13966-13971

Publication/Series

Proceedings of the National Academy of Sciences

Volume

104

Issue

35

Document type

Journal article

Publisher

National Acad Sciences

Topic

  • Basic Medicine
  • Clinical Medicine
  • Other Clinical Medicine

Keywords

  • fluid pressure
  • interstitial
  • inflammation
  • tumor physiology
  • physiology
  • TGF-beta

Status

Published

Research group

  • Åke Oldberg´s group

ISBN/ISSN/Other

  • ISSN: 1091-6490