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

Oldberg, Åke LU ; Kalamajski, Sebastian LU ; Salnikov, Alexei LU ; Stuhr, Linda; Mörgelin, Matthias LU ; Reed, Rolf; Heldin, Nils-Erik and Rubin, Kristofer LU (2007) In Proceedings of the National Academy of Sciences 104(35). p.13966-13971
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fluid pressure, interstitial, inflammation, tumor physiology, physiology, TGF-beta
in
Proceedings of the National Academy of Sciences
volume
104
issue
35
pages
13966 - 13971
publisher
National Acad Sciences
external identifiers
  • wos:000249187500022
  • scopus:35348839617
ISSN
1091-6490
DOI
10.1073/pnas.0702014104
language
English
LU publication?
yes
id
f8dd6d86-c095-4d50-8ed0-442972bba63e (old id 606673)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17715296&dopt=Abstract
date added to LUP
2007-12-19 10:19:04
date last changed
2017-09-03 03:57:52
@article{f8dd6d86-c095-4d50-8ed0-442972bba63e,
  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.},
  author       = {Oldberg, Åke and Kalamajski, Sebastian and Salnikov, Alexei and Stuhr, Linda and Mörgelin, Matthias and Reed, Rolf and Heldin, Nils-Erik and Rubin, Kristofer},
  issn         = {1091-6490},
  keyword      = {fluid pressure,interstitial,inflammation,tumor physiology,physiology,TGF-beta},
  language     = {eng},
  number       = {35},
  pages        = {13966--13971},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma.},
  url          = {http://dx.doi.org/10.1073/pnas.0702014104},
  volume       = {104},
  year         = {2007},
}