Cell plasticity in cancer cell populations

Abstract

In this review, we propose a recension of biological observations on plasticity in cancer cell populations and discuss theoretical considerations about their mechanisms.

Keywords: Cancer; Modelling; Plasticity.

Figure 1.. Summary of cell plasticity models.

( A) Four scenarios of cell plasticity represent the current models and challenges. ( B–E) Potential mechanisms of cell plasticity on different levels. (B) On the chromatin level, epigenetic regulators and DNA elements are shown to be involved in tumour cell tolerance to chemotherapy. (C) On the cellular level, intracellular signalling pathways sensing diverse environmental cues reprogram the transcriptional landscape, leading to adaptation to drug exposures. (D) On the microenvironmental level, inter-cellular communications build up a ‘safe haven’ by direct cell-to-cell interactions and by ‘quorum sensing’ mechanisms. (E) Psychological distress remotely controls tumour cell adaptation by secreting systemic neurotrophic factors. Ac, ; BDNF, Brain-derived neurotrophic factor; BRAF, Proto-Oncogene B-Raf; CAF, Cancer-associated fibroblast; CBP, CREB Binding Protein; EMT, Epithelial-to-Mesenchymal transition; FAK, Focal Adhesion Kinase; GR, Growth factor; HDAC, Histone deacetylases; HGF, Hepatocyte Growth Factor; IFNγ, Interferon gamma; KDM, Lysine demethylases; Me, Methylation; SETDB, SET Domain Bifurcated Histone Lysine Methyltransferase; SMAD, Mothers Against Decapentaplegic Homolog; TEAD, Transcriptional Enhancer Factor TEF; TGF-β, Transforming growth factor beta; TRPA1, Transient Receptor Potential Cation Channel Subfamily A Member 1; TSC22D3, Glucocorticoid-Induced Leucine Zipper Protein; YAP/TAZ, Yes Associated Protein/ Transcriptional Coactivator With PDZ-Binding Motif; ZEB1, Zinc Finger E-Box Binding Homeobox 1.

Figure 2.. Referenced mathematical models of cell populations take cell plasticity into account by making use of ordinary differential equations (A), agent-based models (B) and phenotype-structured partial differential equations (C–F).

Here, we present only the dynamics, not the initial or the boundary conditions, of the models. These models are chosen to be simple on purpose since they are all meant to provide a theoretical framework for therapeutic control and its optimisation. In particular, we do not present large systems of ordinary differential equations or large molecular networks, which nonetheless are referenced in the text. DTEP, Drug tolerant expanded persister; DTP, Drug tolerant persister; HSC, Hematopoetic stem cell; LSC, Leukemic stem cell; R, Resistant cell; S, Sensitive cell.