Cellular interactions constrain tumor growth

Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):1918-1923. doi: 10.1073/pnas.1804150116. Epub 2019 Jan 23.


A tumor is made up of a heterogeneous collection of cell types, all competing on a fitness landscape mediated by microenvironmental conditions that dictate their interactions. Despite the fact that much is known about cell signaling, cellular cooperation, and the functional constraints that affect cellular behavior, the specifics of how these constraints (and the range over which they act) affect the macroscopic tumor growth laws that govern total volume, mass, and carrying capacity remain poorly understood. We develop a statistical mechanics approach that focuses on the total number of possible states each cell can occupy and show how different assumptions on correlations of these states give rise to the many different macroscopic tumor growth laws used in the literature. Although it is widely understood that molecular and cellular heterogeneity within a tumor is a driver of growth, here we emphasize that focusing on the functional coupling of states at the cellular level is what determines macroscopic growth characteristics.

Keywords: cell coupling; statistical mechanics; tumor growth laws; tumor heterogeneity.

MeSH terms

  • Biodiversity
  • Cell Communication / physiology*
  • Cell Enlargement*
  • Humans
  • Models, Biological*
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Signal Transduction / physiology
  • Tumor Microenvironment / physiology