Structural adaptation and heterogeneity of normal and tumor microvascular networks

Axel R. Pries, Annemiek J M Cornelissen, Anoek A. Sloot, Marlene Hinkeldey, Matthew R. Dreher, Michael Höpfner, Mark W. Dewhirst, Timothy W Secomb

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Relative to normal tissues, tumor microcirculation exhibits high structural and functional heterogeneity leading to hypoxic regions and impairing treatment efficacy. Here, computational simulations of blood vessel structural adaptation are used to explore the hypothesis that abnormal adaptive responses to local hemodynamic and metabolic stimuli contribute to aberrant morphological and hemodynamic characteristics of tumor microcirculation. Topology, vascular diameter, length, and red blood cell velocity of normal mesenteric and tumor vascular networks were recorded by intravital microscopy. Computational models were used to estimate hemodynamics and oxygen distribution and to simulate vascular diameter adaptation in response to hemodynamic, metabolic and conducted stimuli. The assumed sensitivity to hemodynamic and conducted signals, the vascular growth tendency, and the random variability of vascular responses were altered to simulate 'normal' and 'tumor' adaptation modes. The heterogeneous properties of vascular networks were characterized by diameter mismatch at vascular branch points (d3var) and deficit of oxygen delivery relative to demand (O2def). In the tumor, d3 var and O2def were higher (0.404 and 0.182) than in normal networks (0.278 and 0.099). Simulated remodeling of the tumor network with 'normal' parameters gave low values (0.288 and 0.099). Conversely, normal networks attained tumor-like characteristics (0.41 and 0.179) upon adaptation with 'tumor' parameters, including low conducted sensitivity, increased growth tendency, and elevated random biological variability. It is concluded that the deviant properties of tumor microcirculation may result largely from defective structural adaptation, including strongly reduced responses to conducted stimuli.

Original languageEnglish (US)
Article numbere1000394
JournalPLoS Computational Biology
Volume5
Issue number5
DOIs
StatePublished - May 2009

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Microvessels
tumor
blood vessels
Tumors
Tumor
Blood Vessels
Hemodynamics
neoplasms
hemodynamics
Microcirculation
Neoplasms
Oxygen
blood
oxygen
Remodeling
Red Blood Cells
Branch Point
Computational Simulation
Blood vessels
Growth

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

Pries, A. R., Cornelissen, A. J. M., Sloot, A. A., Hinkeldey, M., Dreher, M. R., Höpfner, M., ... Secomb, T. W. (2009). Structural adaptation and heterogeneity of normal and tumor microvascular networks. PLoS Computational Biology, 5(5), [e1000394]. https://doi.org/10.1371/journal.pcbi.1000394

Structural adaptation and heterogeneity of normal and tumor microvascular networks. / Pries, Axel R.; Cornelissen, Annemiek J M; Sloot, Anoek A.; Hinkeldey, Marlene; Dreher, Matthew R.; Höpfner, Michael; Dewhirst, Mark W.; Secomb, Timothy W.

In: PLoS Computational Biology, Vol. 5, No. 5, e1000394, 05.2009.

Research output: Contribution to journalArticle

Pries, AR, Cornelissen, AJM, Sloot, AA, Hinkeldey, M, Dreher, MR, Höpfner, M, Dewhirst, MW & Secomb, TW 2009, 'Structural adaptation and heterogeneity of normal and tumor microvascular networks', PLoS Computational Biology, vol. 5, no. 5, e1000394. https://doi.org/10.1371/journal.pcbi.1000394
Pries AR, Cornelissen AJM, Sloot AA, Hinkeldey M, Dreher MR, Höpfner M et al. Structural adaptation and heterogeneity of normal and tumor microvascular networks. PLoS Computational Biology. 2009 May;5(5). e1000394. https://doi.org/10.1371/journal.pcbi.1000394
Pries, Axel R. ; Cornelissen, Annemiek J M ; Sloot, Anoek A. ; Hinkeldey, Marlene ; Dreher, Matthew R. ; Höpfner, Michael ; Dewhirst, Mark W. ; Secomb, Timothy W. / Structural adaptation and heterogeneity of normal and tumor microvascular networks. In: PLoS Computational Biology. 2009 ; Vol. 5, No. 5.
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