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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

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Author

  • Tomas Friman
  • Renata Gustafsson
  • Linda B. Stuhr
  • Jean Chidiac
  • Nils-Erik Heldin
  • Rolf K. Reed
  • Åke Oldberg
  • Kristofer Rubin

Summary, in English

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.

Department/s

  • Åke Oldberg´s group

Publishing year

2012

Language

English

Publication/Series

PLoS ONE

Volume

7

Issue

3

Document type

Journal article

Publisher

Public Library of Science (PLoS)

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Åke Oldberg´s group

ISBN/ISSN/Other

  • ISSN: 1932-6203