AMIGOS - Hypoxia

Modeling Tumor in Hypoxic Condition

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Version 1.0 - published on 25 Apr 2019

doi:10.21981/G7YF-VC25 cite this

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Abstract

Biological Background

  • Hypoxic conditions occur in the center of tumor after tumor cells use and deplete oxygen.
  • Hypoxic cells secrete signaling chemicals to induce vascularization, such as vascular epithelial growth factor (VEGF).

Methods

  • This model is developed with using agentbased multicellular system simulator which is called PhysiCell [1].
  • Cells are changing behavior according to oxygen level. After they become hypoxic, their genes are regulated.
  • Our model accounts for this vascularization by increasing VEGF secretion by hypoxic cells.
  • Vasculature is controlled by three mechanisms, which are grow, death, and advective flux.
  • Blood supplies or uptakes metabolites from microenvironment according to blood target values.

Results

  • Tumor has a necrotic core that has nearly no oxygen.
  • Cellular layering is formed as: Necrotic (purple), Hypoxic (Green), Normoxic(Red)
  • VEGF concentration through tumor has ring-like distribution which is consistent with literature 3
  • A small vasculature accumulation near to tumor is observed. This was an expected behavior in order to modeling equations.

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Sponsored by

National Science Foundation (Award 1720625)

National Institutes of Health (U01-CA232137-01)

Breast Cancer Research Foundation

Jayne Koskinas Ted Giovanis Foundation for Health and Policy

References

 [1] PhysiCell: An open source physics-based cell simulator for 3-D multicellular systems. Ghaffarizadeh A, Heiland R, Friedman SH, Mumenthaler SM, Macklin P. PLOS Computational Biology 14(2): e1005991. doi: 10.1371/journal.pcbi.1005991 (2018)

[2] xml2jupyter: Mapping parameters between XML and Jupyter widges. Heiland R, Mishler D, Zhang T, Bower E, Macklin P. bioRxiv 601211; doi: 10.1101/601211 (2019)

[3] Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies C Voutouri, N D. Kirkpatrick, E Chung, F Mpekris, J W. Baish, L L. Munn, D Fukumura, T Stylianopoulos, R K. Jain: PNAS: https://doi.org/10.1073/pnas.1818322116

Cite this work

Researchers should cite this work as follows:

  • Furkan Kurtoglu, John Metzcar, Paul Macklin, Randy Heiland (2019), "AMIGOS - Hypoxia," http://nanohub.org/resources/hypoxia19. (DOI: 10.21981/G7YF-VC25).

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