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Increased Fibrosis and Interstitial Fluid Pressure in Two Different Types of Syngeneic Murine Carcinoma Grown in Integrin beta 3-Subunit Deficient Mice

Friman, Tomas; Gustafsson, Renata LU ; Stuhr, Linda B.; Chidiac, Jean; Heldin, Nils-Erik; Reed, Rolf K.; Oldberg, Åke LU and Rubin, Kristofer (2012) In PLoS ONE 7(3).
Abstract
Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that alpha(V)beta(3) expressed by stromal cells is involved in the control of interstitial fluid pressure (IFP), extracellular volume (ECV) and collagen scaffold architecture in experimental murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and LM3 mammary carcinomas grown in integrin beta(3)-deficient compared to wild-type BALB/ c mice. Integrin beta(3)-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin beta(3)-deficient mice revealed a coarser and denser collagen network compared to carcinomas in... (More)
Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that alpha(V)beta(3) expressed by stromal cells is involved in the control of interstitial fluid pressure (IFP), extracellular volume (ECV) and collagen scaffold architecture in experimental murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and LM3 mammary carcinomas grown in integrin beta(3)-deficient compared to wild-type BALB/ c mice. Integrin beta(3)-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin beta(3)-deficient mice revealed a coarser and denser collagen network compared to carcinomas in wild-type littermates. Collagen fibers were built from heterogeneous and thicker collagen fibrils in carcinomas from integrin beta(3)-deficient mice. The fibrotic extracellular matrix (ECM) did not correlate with increased macrophage infiltration in integrin beta(3)-deficient mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated by increased inflammation. In conclusion, we report that integrin beta(3)-deficiency in tumor stroma led to an elevated IFP and lowered ECV that correlated with a more fibrotic ECM, underlining the role of the collagen network for carcinoma physiology. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
7
issue
3
publisher
Public Library of Science
external identifiers
  • wos:000305339100116
  • scopus:84859127476
ISSN
1932-6203
DOI
10.1371/journal.pone.0034082
language
English
LU publication?
yes
id
1e38ad93-87b3-4f12-a061-1d8322ac5cdd (old id 2890908)
date added to LUP
2012-08-01 08:54:50
date last changed
2017-08-27 04:39:21
@article{1e38ad93-87b3-4f12-a061-1d8322ac5cdd,
  abstract     = {Stroma properties affect carcinoma physiology and direct malignant cell development. Here we present data showing that alpha(V)beta(3) expressed by stromal cells is involved in the control of interstitial fluid pressure (IFP), extracellular volume (ECV) and collagen scaffold architecture in experimental murine carcinoma. IFP was elevated and ECV lowered in syngeneic CT26 colon and LM3 mammary carcinomas grown in integrin beta(3)-deficient compared to wild-type BALB/ c mice. Integrin beta(3)-deficiency had no effect on carcinoma growth rate or on vascular morphology and function. Analyses by electron microscopy of carcinomas from integrin beta(3)-deficient mice revealed a coarser and denser collagen network compared to carcinomas in wild-type littermates. Collagen fibers were built from heterogeneous and thicker collagen fibrils in carcinomas from integrin beta(3)-deficient mice. The fibrotic extracellular matrix (ECM) did not correlate with increased macrophage infiltration in integrin beta(3)-deficient mice bearing CT26 tumors, indicating that the fibrotic phenotype was not mediated by increased inflammation. In conclusion, we report that integrin beta(3)-deficiency in tumor stroma led to an elevated IFP and lowered ECV that correlated with a more fibrotic ECM, underlining the role of the collagen network for carcinoma physiology.},
  author       = {Friman, Tomas and Gustafsson, Renata and Stuhr, Linda B. and Chidiac, Jean and Heldin, Nils-Erik and Reed, Rolf K. and Oldberg, Åke and Rubin, Kristofer},
  issn         = {1932-6203},
  language     = {eng},
  number       = {3},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Increased Fibrosis and Interstitial Fluid Pressure in Two Different Types of Syngeneic Murine Carcinoma Grown in Integrin beta 3-Subunit Deficient Mice},
  url          = {http://dx.doi.org/10.1371/journal.pone.0034082},
  volume       = {7},
  year         = {2012},
}