Non-cell-autonomous effects yield lower clonal diversity in expanding tumors

Authored by Benjamin Roche, Tazzio Tissot, Frederic Thomas

Date Published: 2017

DOI: 10.1038/s41598-017-11562-w

Sponsors: No sponsors listed

Platforms: No platforms listed

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

Recent cancer research has investigated the possibility that non-cell-autonomous (NCA) driving tumor growth can support clonal diversity (CD). Indeed, mutations can affect the phenotypes not only of their carriers ({''}cell-autonomous{''}, CA effects), but also sometimes of other cells (NCA effects). However, models that have investigated this phenomenon have only considered a restricted number of clones. Here, we designed an individual-based model of tumor evolution, where clones grow and mutate to yield new clones, among which a given frequency have NCA effects on other clones' growth. Unlike previously observed for smaller assemblages, most of our simulations yield lower CD with high frequency of mutations with NCA effects. Owing to NCA effects increasing competition in the tumor, clones being already dominant are more likely to stay dominant, and emergent clones not to thrive. These results may help personalized medicine to predict intratumor heterogeneity across different cancer types for which frequency of NCA effects could be quantified.

Tags

glioblastoma evolutionary dynamics progression invasion growth Mathematical-model Driver Cancer stem-cells Intratumor heterogeneity Carcinogenesis