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

Research output: Contribution to journalArticle

Abstract

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.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Basic Medicine
  • Clinical Medicine
  • Other Clinical Medicine

Keywords

  • fluid pressure, interstitial, inflammation, tumor physiology, physiology, TGF-beta
Original languageEnglish
Pages (from-to)13966-13971
JournalProceedings of the National Academy of Sciences
Volume104
Issue number35
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division III (013230700), Division V (013230900), Department of Experimental Medical Science (013210000), Åke Oldberg´s group (013212049), Oncology, MV (013035000), Connective Tissue Biology (013230151), Division of Infection Medicine (BMC) (013024020)

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