Intercellular adhesion and cancer invasion: a discrete simulation using the extended Potts model

Area of Science:

• Computational Biology
• Biophysics
• Cancer Research

Background:

• Malignant invasion is a complex process driven by cell interactions and environmental cues.
• Understanding the biophysical factors influencing tumor cell invasion is crucial for developing effective therapies.

Purpose of the Study:

• To investigate the influence of cell-cell and cell-medium adhesion on malignant invasion using a thermodynamic model.
• To explore the synergistic effects of proteolytic enzyme secretion and haptotaxis on tumor invasion.
• To analyze the role of cell proliferation in the invasion process, considering varying adhesiveness.

Main Methods:

• Development of a discrete thermodynamic model, extending the Potts model.
• Simulation of malignant cell populations with homotypic and heterotypic adhesion.
• Inclusion of proteolytic enzyme secretion and haptotactic gradients.
• Incorporation of a proliferation algorithm linked to adhesiveness changes.

Main Results:

• Tumor invasion morphology and invasiveness are significantly influenced by cell adhesion parameters.
• Cell-medium adhesion plays a more critical role in invasion than cell-cell adhesion.
• Increased proteolytic enzyme secretion and haptotaxis synergistically enhance tumor invasion.
• Cell proliferation can increase invasion depth but may also reduce invasiveness under certain conditions.

Conclusions:

• Cell adhesion dynamics are key determinants of malignant invasion patterns.
• Targeting cell-medium adhesion may be a viable therapeutic strategy.
• Combined strategies enhancing enzyme secretion and haptotaxis can promote invasion, while proliferation's effect is context-dependent.