Computational model of the first steps in bladder cancer development

The mechanical properties of cells and extracellular environment, in particular their stiffness and adhesion capacity, are important in the early stages of bladder cancer initiation. A computational model, developed at the University of Coimbra, describes the different layers of the urothelium and allows to study which characteristics are most relevant to the invasive capacity of neighboring tissues by tumor cells. This work provides useful indications for the development of alternative therapeutic strategies. 

Authors and Affiliations:

João Carvalho, Valéria Lopes, Rui Travasso

CFisUC, Department of Physics, University of Coimbra, Coimbra, Portugal

Abstract:

Bladder cancer is one of the most common types of cancer , being the sixth more frequent in men, and one with higher recurrence rates and overall treatment costs. We introduce an agent-based computational model of the urothelium, adopting a Cellular Potts Model (CPM) approach to describe both a healthy urothelium and the development of bladder cancer. We focus on the identification of the conditions in which cancer cells cross, by mechanical means, the basement membrane and invade the bladder lamina propria. When within the urothelium the tumor grows in a very constrained environment. These tight conditions imply that the urothelium layer where the tumor initiates greatly determines tumor growth and invasiveness. Moreover, we demonstrate how specific mechanical properties of the cancer cells, as their stiffness or the adhesion to neighboring cells, heavily modulate the critical initial moments of tumor development. We propose that these characteristics should be considered as therapeutic targets to control tumor growth.

Journal:

International Journal for Numerical Methods in Biomedical Engineering

Link:

https://onlinelibrary.wiley.com/doi/epdf/10.1002/cnm.3417