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Microenvironment driven invasion: a multiscale multimodel investigation

  • Alexander R. A. Anderson
  • Katarzyna A. Rejniak
  • Philip Gerlee
  • Vito Quaranta
Article

Abstract

Cancer is a complex, multiscale process, in which genetic mutations occurring at a subcellular level manifest themselves as functional and morphological changes at the cellular and tissue scale. The importance of interactions between tumour cells and their microenvironment is currently of great interest in experimental as well as computational modelling. Both the immediate microenvironment (e.g. cell–cell signalling or cell–matrix interactions) and the extended microenvironment (e.g. nutrient supply or a host tissue structure) are thought to play crucial roles in both tumour progression and suppression. In this paper we focus on tumour invasion, as defined by the emergence of a fingering morphology, which has previously been shown to be dependent upon harsh microenvironmental conditions. Using three different modelling approaches at two different spatial scales we examine the impact of nutrient availability as a driving force for invasion. Specifically we investigate how cell metabolism (the intrinsic rate of nutrient consumption and cell resistance to starvation) influences the growing tumour. We also discuss how dynamical changes in genetic makeup and morphological characteristics, of the tumour population, are driven by extreme changes in nutrient supply during tumour development. The simulation results indicate that aggressive phenotypes produce tumour fingering in poor nutrient, but not rich, microenvironments. The implication of these results is that an invasive outcome appears to be co-dependent upon the evolutionary dynamics of the tumour population driven by the microenvironment.

Mathematics Subject Classification (2000)

82B24 92C15 92C17 92B20 92D05 76Z99 92C37 92C50 

Supplementary material

285_2008_210_MOESM1_ESM.zip (8.2 mb)
ESM 1 (ZIP 8367 kb)

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Alexander R. A. Anderson
    • 1
    • 2
  • Katarzyna A. Rejniak
    • 1
    • 2
  • Philip Gerlee
    • 1
    • 3
  • Vito Quaranta
    • 4
  1. 1.Division of MathematicsUniversity of DundeeDundeeScotland, UK
  2. 2.Integrated Mathematical OncologyMoffitt Cancer Center and Research InstituteTampaUSA
  3. 3.Center for Models of LifeNiels Bohr InstituteKøbenhavn ØDenmark
  4. 4.Department of Cancer BiologyVanderbilt University School of MedicineNashvilleUSA

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