Modeling Tumor Angiogenesis with Cellular Automata

TL;DR

This paper presents a 2D cellular automata model to simulate tumor angiogenesis, capturing key behaviors like sprout growth, branching, and anastomoses, highlighting chemotaxis as the dominant factor.

Contribution

It introduces a novel CA-based simulation framework that models complex angiogenic behaviors, including sprout branching and fusion, in tumor growth.

Findings

Chemotaxis is the most effective driving force for angiogenesis.

Sprouts tend to branch more as they approach the tumor.

No two sprouts originate from adjacent locations.

Abstract

Angiogenesis is the formation of new blood vessels from the existing vessels. During tumour angiogenesis, tumour cells secret a number of chemical substrates called tumour angiogenic factors (TAFs). These factors diffuse through the extracellular matrix (ECM) and degrade the basement membrane of nearby vasculature. The TAFs also disrupt the corresponding endothelial cell receptors and form finger like capillary sprouts. These factors also create a chemical gradient (chemotaxis) between the tumour and the surrounding blood vessels. Due to the chemotactic force, the capillary sprouts migrate towards the tumour. On the other hand, a haptotactic force generated due to fibronectin which is secreted by the endothelial cell, also acts on these sprouts. These sprouts grow through the proliferation of recruited endothelial cells from the parent vessels. Tumour angiogenesis is not fully understood yet. In this paper, we use 2-D cellular automata (CA) model to study the behavior of tumour angiogenesis using both Moore and von-Neumann neighborhood. The CA model also mimics capillary sprout branching and the fusion of two adjacent sprout tips (anastomoses). In this simulation, a couple of important points are noted: a) no two capillary sprouts are generated from adjacent locations; b) as the sprouts approach closer to the tumour, its branching tendency increases; c) chemotaxis is the most effective driving force for angiogenesis.