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Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2007 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 104, no 35, 13966-13971 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 104, no 35, 13966-13971 p.
Keyword [en]
Inflammation, Interstitial fluid pressure, Physiology, TGF-β, Tumor physiology
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-15819DOI: 10.1073/pnas.0702014104ISI: 000249187500022PubMedID: 17715296OAI: oai:DiVA.org:uu-15819DiVA: diva2:43590
Available from: 2008-03-06 Created: 2008-03-06 Last updated: 2017-12-08Bibliographically approved

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Heldin, Nils-ErikRubin, Kristofer

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Department of Medical Biochemistry and MicrobiologyDepartment of Genetics and Pathology
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