A three dimensional computer model of urothelium and bladder cancer initiation, progress and collective invasion

Abstract

Bladder cancer is a common type of cancer, and one with high recurrence rate and overall monitoring and treatment costs. It was developed and tested a three-dimensional agent-based computational model of the urothelium, a purpose-built Cellular Potts Model, to describe both a healthy urothelium and the initiation, development and invasion stages of a bladder cancer. This work is focused on the identification of the conditions in which tumor cells can cross, by mechanical means, the basement membrane and invade the bladder lamina propria. It is demonstrated how specific mechanical properties of the cancer cells, as their stiffness and adhesion to neighboring cells, heavily determine the probability of transition from a non-invasive to an invasive tumor. In particular, it is shown how an increased cellular adhesion of tumor cells to neighbor cells and/or extracellular fibers drives a collective migration, increasing the tumor growth rate and its invasion capacity. It is proposed that these physical characteristics should be considered as potential therapeutic targets to control the tumor growth and its progress to a more dangerous condition.

Keywords

• Bladder cancer
• Cellular Potts Model
• Collective invasion
• Cell adhesion
• Cell mechanics
• Cancer therapeutics