Role of the Interplay Between the Internal and External Conditions in Invasive Behavior of Tumors

TL;DR

This paper introduces a new model to explore how cancer stem cell density and oxygen levels influence tumor invasiveness, highlighting the importance of internal and external interactions in tumor progression.

Contribution

It presents a novel model beyond standard stochastic approaches, emphasizing the role of natural selection and the interplay of internal and external factors in tumor invasion.

Findings

Tumor invasiveness depends on cancer stem cell density and oxygen levels.

Natural selection explains complex tumor morphology.

Interplay between internal and external conditions influences tumor behavior.

Abstract

Tumor growth, which plays a central role in cancer evolution, depends on both the internal features of the cells, such as their ability for unlimited duplication, and the external conditions, e.g., supply of nutrients, as well as the dynamic interactions between the two. A stem cell theory of cancer has recently been developed that suggests the existence of a subpopulation of self-renewing tumor cells which is responsible for tumorigenesis, and is able to initiate metastatic spreading. The question of abundance of the cancer stem cells (CSCs) and its relation to tumor malignancy has, however, remained an unsolved problem and has been a subject of recent debates. In this paper, we propose a novel model beyond the standard stochastic models of tumor development, in order to explore the effect of the density of the CSCs and oxygen on the tumor's invasive behavior. The model identifies natural selection as the underlying process for complex morphology of tumors, which has been observed experimentally, and indicates that their invasive behavior depends on {\it both} the number of the CSCs and the oxygen density in the microenvironment. The interplay between the external and internal conditions may pave the way for a new cancer therapy.