Mathematical model of heterogeneous cancer growth with an autocrine signalling pathway

Cell Prolif. 2012 Oct;45(5):445-55. doi: 10.1111/j.1365-2184.2012.00835.x. Epub 2012 Jul 11.

Abstract

Objectives: Cancer is a complex biological occurrence which is difficult to describe clearly and explain its growth development. As such, novel concepts, such as of heterogeneity and signalling pathways, grow exponentially and many mathematical models accommodating the latest knowledge have been proposed. Here, we present a simple mathematical model that exhibits many characteristics of experimental data, using prostate carcinoma cell spheroids under treatment.

Materials and methods: We have modelled cancer as a two-subpopulation system, with one subpopulation representing a cancer stem cell state, and the other a normal cancer cell state. As a first approximation, these follow a logistical growth model with self and competing capacities, but they can transform into each other by using an autocrine signalling pathway.

Results and conclusion: By analysing regulation behaviour of each of the system parameters, we show that the model exhibits many characteristics of actual cancer growth curves. Features reproduced in this model include delayed phase of evolving cancer under 17AAG treatment, and bi-stable behaviour under treatment by irradiation. In addition, our interpretation of the system parameters corresponds well with known facts involving 17AAG treatment. This model may thus provide insight into some of the mechanisms behind cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autocrine Communication / drug effects
  • Autocrine Communication / physiology*
  • Autocrine Communication / radiation effects
  • Benzoquinones / pharmacology
  • Cell Proliferation* / drug effects
  • Cell Proliferation* / radiation effects
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • Humans
  • Lactams, Macrocyclic / pharmacology
  • Logistic Models
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Phenotype
  • Radiation Dosage
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Signal Transduction / radiation effects

Substances

  • Benzoquinones
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • tanespimycin