Exploring the relationship between vascular remodelling and tumour growth using agent-based modelling.

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.