Characterising Cancer Cell Responses to Cyclic Hypoxia Using Mathematical Modelling.

Autor: Celora GL; Department of Mathematics, University College London, Gordon Street, London, 100190, UK. g.celora@ucl.ac.uk., Nixson R; Mathematical Institute, University of Oxford, Andrew Wiles Building, Woodstock Rd, Oxford, OX2 6GG, UK., Pitt-Francis JM; Department of Computer Science, University of Oxford, Parks Rd, Oxford, OX1 3QD, UK., Maini PK; Mathematical Institute, University of Oxford, Andrew Wiles Building, Woodstock Rd, Oxford, OX2 6GG, UK., Byrne HM; Mathematical Institute, University of Oxford, Andrew Wiles Building, Woodstock Rd, Oxford, OX2 6GG, UK.; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, UK.
Jazyk: angličtina
Zdroj: Bulletin of mathematical biology [Bull Math Biol] 2024 Nov 06; Vol. 86 (12), pp. 145. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.1007/s11538-024-01359-0
Abstrakt: In vivo observations show that oxygen levels in tumours can fluctuate on fast and slow timescales. As a result, cancer cells can be periodically exposed to pathologically low oxygen levels; a phenomenon known as cyclic hypoxia. Yet, little is known about the response and adaptation of cancer cells to cyclic, rather than, constant hypoxia. Further, existing in vitro models of cyclic hypoxia fail to capture the complex and heterogeneous oxygen dynamics of tumours growing in vivo. Mathematical models can help to overcome current experimental limitations and, in so doing, offer new insights into the biology of tumour cyclic hypoxia by predicting cell responses to a wide range of cyclic dynamics. We develop an individual-based model to investigate how cell cycle progression and cell fate determination of cancer cells are altered following exposure to cyclic hypoxia. Our model can simulate standard in vitro experiments, such as clonogenic assays and cell cycle experiments, allowing for efficient screening of cell responses under a wide range of cyclic hypoxia conditions. Simulation results show that the same cell line can exhibit markedly different responses to cyclic hypoxia depending on the dynamics of the oxygen fluctuations. We also use our model to investigate the impact of changes to cell cycle checkpoint activation and damage repair on cell responses to cyclic hypoxia. Our simulations suggest that cyclic hypoxia can promote heterogeneity in cellular damage repair activity within vascular tumours.
(© 2024. The Author(s).)
Databáze: MEDLINE
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