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

First Author  Oldberg A Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  35 Pages  13966-71
PubMed ID  17715296 Mgi Jnum  J:306040
Mgi Id  MGI:6708088 Doi  10.1073/pnas.0702014104
Citation  Oldberg A, et al. (2007) Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma. Proc Natl Acad Sci U S A 104(35):13966-71
abstractText  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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