A cell-based model for analyzing growth and invasion of tumor spheroids

Abstract

Both chemical and mechanical determinants adapt and react throughout the process of tumor invasion. In this study, a cell-based model is used to uncover the growth and invasion of a three-dimensional solid tumor confined within normal cells. Each cell is treated as a spheroid that can deform, migrate, and proliferate. Some fundamental aspects of tumor development are considered, including normal tissue constraints, active cellular motility, homotypic and heterotypic intercellular interactions, and pressure-regulated cell division as well. It is found that differential motility between cancerous and normal cells tends to break the spheroidal symmetry, leading to a finger instability at the tumor rim, while stiff normal cells inhibit tumor branching and favor uniform tumor expansion. The heterotypic cell-cell adhesion is revealed to affect the branching geometry. Our results explain many experimental observations, such as fingering invasion during tumor growth, stiffness inhibition of tumor invasion, and facilitation of tumor invasion through cancerous-normal cell adhesion. This study helps understand how cellular events are coordinated in tumor morphogenesis at the tissue level.