Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
Date
2023
Authors
Murphy, R.J.
Gunasingh, G.
Haass, N.K.
Simpson, M.J.
Editors
Maini, P.K.
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Journal article
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PLoS Computational Biology, 2023; 19(1, article no. e1010833):1-29
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Abstract
Tumours are subject to external environmental variability. However, in vitro tumour spheroid experiments, used to understand cancer progression and develop cancer therapies, have been routinely performed for the past fifty years in constant external environments. Furthermore, spheroids are typically grown in ambient atmospheric oxygen (normoxia), whereas most in vivo tumours exist in hypoxic environments. Therefore, there are clear discrepancies between in vitro and in vivo conditions. We explore these discrepancies by combining tools from experimental biology, mathematical modelling, and statistical uncertainty quantification. Focusing on oxygen variability to develop our framework, we reveal key biological mechanisms governing tumour spheroid growth. Growing spheroids in time-dependent conditions, we identify and quantify novel biological adaptation mechanisms, including unexpected necrotic core removal, and transient reversal of the tumour spheroid growth phases.
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Copyright 2023 The author(s) (https://creativecommons.org/licenses/by/4.0/)
Access Condition Notes: This is an open access article distributed under the terms of the Creative Commons Attribution License