Collagen-binding proteoglycan fibromodulin can determine stroma matrix structure and fluid balance in experimental carcinoma.
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.
Oldberg
Ake
A
Department of Experimental Medical Sciences, BMC, B-12, University of Lund, SE-221 84 Lund, Sweden.
Kalamajski
Sebastian
S
Salnikov
Alexei V
AV
Stuhr
Linda
L
Mörgelin
Matthias
M
Reed
Rolf K
RK
Heldin
Nils-Erik
NE
Rubin
Kristofer
K
D000818:Animals; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D045604:Extracellular Fluid / Q000502:physiology; D005109:Extracellular Matrix / Q000473:pathology / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071235:Fibromodulin; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology
D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D011509:Proteoglycans; D000071235:Fibromodulin; D003094:Collagen
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