Diversity of Dynamics and Morphologies of Invasive Solid Tumors

TL;DR

This study extends a cellular automaton model to include pressure effects, revealing how microenvironment heterogeneity and mechanical forces influence tumor morphology and invasiveness, with implications for cancer treatment strategies.

Contribution

We incorporate pressure effects into a tumor growth model, demonstrating how mechanical forces and heterogeneity affect tumor shape and invasion patterns.

Findings

High pressure and heterogeneity promote finger-like tumor protrusions.

Invasive cells degrade extracellular matrix, reducing fingering growth.

Soft, homogeneous environments lead to more isotropic tumor shapes.

Abstract

Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol. 7, e1002314 (2011)] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due to the deformation of the microenvironment and its effect on the local tumor-host interface instability. Both noninvasive-proliferative growth and invasive growth with individual cells that detach themselves from the primary tumor and migrate into the surrounding microenvironment are investigated. We find that while noninvasive tumors growing in "soft" homogeneous microenvironments develop almost isotropic shapes, both high pressure and host heterogeneity can strongly enhance malignant behavior, leading to finger-like protrusions of the tumor surface. Moreover, we show that individual invasive cells of an invasive tumor degrade the local extracellular matrix at the tumor-host interface, which diminishes the fingering growth of the primary tumor. The implications of our results for cancer diagnosis, prognosis and therapy are discussed.