Proliferation as a natural strategy to suppress neoplasia.

Abstract

Cell proliferation is necessary to maintain tissue homeostasis, but proliferation carries with it a risk of cancer. To understand how some organisms suppress cancer while maintaining homeostasis, we developed a dynamical model of cell populations. The model identifies two regimes. In one regime, as expected, proliferation drives accumulation of neoplastic cells. In another regime, unexpectedly, increasing proliferation suppresses accumulation of neoplastic cells. In this regime, as more cells proliferate, more cells also die as a consequence of homeostatic feedback. As long as neoplastic cells are targeted preferentially, the high flux effectively acts as a proofreader. High-flux proofreading works even when the system lacks a highly specific detector of neoplastic cells. As a first experimental test, we examined the jellyfish. Neoplasms are rarely observed in cnidarians, yet simply inhibiting proliferation promotes neoplasms. The quantitative framework developed here offers experimentally testable predictions to assess high-flux proofreading in other systems.