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Establishing a Physiologic Human Vascularized Micro-Tumor Model for Cancer Research
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Exploring the relationship between vascular remodelling and tumour growth using agent-based modelling.

Nicholas Fan1, Joshua A Bull1, Helen M Byrne1,2

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Mechanical forces from tumor cells compress blood vessels, altering oxygen supply and tumor growth. This vascular remodeling significantly impacts radiotherapy response and regrowth dynamics.

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Area of Science:

  • Computational Biology
  • Biophysics
  • Cancer Research

Background:

  • Tumor growth and response to therapy are influenced by the tumor microenvironment (TME).
  • Mechanical interactions between tumor cells and vasculature play a critical role in oxygen supply and tumor progression.
  • Existing models often lack detailed mechanical coupling between cells and the vascular network.

Purpose of the Study:

  • To investigate how mechanical interactions between tumor cells and vasculature affect tumor oxygenation, growth, and radiotherapy response.
  • To develop and utilize a multiscale agent-based model (ABM) incorporating vessel deformation due to mechanical forces.
  • To quantify the impact of vascular remodeling on tumor characteristics and treatment outcomes.

Main Methods:

  • Development of a multiscale agent-based model (ABM) simulating tumor cell proliferation and mechanical interactions.
  • Incorporation of vessel deformation driven by forces between tumor cells and vessel walls, leading to pressure-induced occlusion.
  • Inclusion of Stokes' drag and a novel friction force representing cell-extracellular matrix (ECM) adhesion resistance to model mechanical interactions.

Main Results:

  • Increased friction force leads to significant vessel compression and altered pressure gradients, unlike Stokes' drag alone.
  • Tumor vascularization, quantified by cross-pair correlation function, is influenced by vascular remodeling and friction parameters.
  • Altered vascular landscapes critically affect tumor oxygenation, morphology, and susceptibility to radiotherapy, impacting post-treatment regrowth.

Conclusions:

  • Mechanical interactions and resultant vascular remodeling are crucial factors in tumor progression and response to radiotherapy.
  • The developed ABM highlights the importance of friction forces in simulating realistic tumor vascular dynamics.
  • Accounting for mechanical forces and vascular remodeling is essential for accurate prediction of tumor behavior and treatment efficacy.