Microenvironmental influence on microtumour infiltration patterns: 3D-mathematical modelling supported by in vitro...

Area of Science:

• Oncology
• Mathematical Biology
• Biophysics

Background:

• Tumor infiltration and spatial organization are complex, influenced by tumor type, stage, and microenvironment.
• Multidisciplinary and individualized approaches are often necessary for accurate cancer research.

Purpose of the Study:

• To develop a 3D mathematical model combining experimental and numerical methods to simulate avascular microtumor growth and infiltration patterns.
• To investigate the impact of different microenvironmental conditions on tumor behavior.

Main Methods:

• A diffusion-convection reaction equation was used, incorporating logistic proliferation, volumetric growth, and invasion.
• Model parameters were fitted to experimental data from multicellular tumor spheroids (MTSs) in collagen I gels.
• Spatially variable radial velocity and diffusion coefficients were introduced using a shape function and a diffusion-limited-aggregation (DLA)-derived fractal matrix.

Main Results:

• Conditioned media from adipocytes/preadipocytes altered MTS infiltration from collective/laminar to individual/atomized patterns.
• Numerical simulations successfully reproduced both infiltration patterns qualitatively and quantitatively.
• Analyses included area quantification, fractal dimensions, lacunarity, and Bland-Altman analysis.

Conclusions:

• The combined experimental/numerical approach provides a robust framework for modeling tumor microenvironment interactions.
• This method has potential applications in both basic cancer research and clinical oncology.
• The model's ability to reproduce diverse infiltration patterns highlights its versatility.