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Systems-Level Modeling of Cancer-Fibroblast Interaction

Author

Listed:
  • Raymond C Wadlow
  • Ben S Wittner
  • S Aidan Finley
  • Henry Bergquist
  • Rabi Upadhyay
  • Stephen Finn
  • Massimo Loda
  • Umar Mahmood
  • Sridhar Ramaswamy

Abstract

Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchymal cells, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may prove useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts.

Suggested Citation

  • Raymond C Wadlow & Ben S Wittner & S Aidan Finley & Henry Bergquist & Rabi Upadhyay & Stephen Finn & Massimo Loda & Umar Mahmood & Sridhar Ramaswamy, 2009. "Systems-Level Modeling of Cancer-Fibroblast Interaction," PLOS ONE, Public Library of Science, vol. 4(9), pages 1-10, September.
    • Handle: RePEc:plo:pone00:0006888
    DOI: 10.1371/journal.pone.0006888
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    References listed on IDEAS

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    1. Neil A. Bhowmick & Eric G. Neilson & Harold L. Moses, 2004. "Stromal fibroblasts in cancer initiation and progression," Nature, Nature, vol. 432(7015), pages 332-337, November.
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