Homeostatic competition drives tumor growth and metastasis nucleation

TL;DR

This paper introduces a homeostatic regulation model explaining tumor growth and metastasis, highlighting the importance of tissue stability and surface effects, and providing insights into metastatic size distribution and preferential growth sites.

Contribution

It presents a novel mechanism based on homeostatic competition that explains metastasis size thresholds, distribution patterns, and the seed and soil hypothesis.

Findings

Metastases require surpassing a critical size to grow.

Size-independent growth rates do not match observed data.

Homeostatic pressure could measure metastatic potential.

Abstract

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths.