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Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability

View ORCID ProfileRyan J. Murphy, View ORCID ProfileGency Gunasingh, View ORCID ProfileNikolas K. Haass, View ORCID ProfileMatthew J. Simpson
doi: https://doi.org/10.1101/2022.04.24.489294
Ryan J. Murphy
1Mathematical Sciences, Queensland University of Technology, Brisbane, Australia
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  • For correspondence: r23.murphy@qut.edu.au
Gency Gunasingh
2The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia
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Nikolas K. Haass
2The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia
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Matthew J. Simpson
1Mathematical Sciences, Queensland University of Technology, Brisbane, Australia
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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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 24, 2022.
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Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
Ryan J. Murphy, Gency Gunasingh, Nikolas K. Haass, Matthew J. Simpson
bioRxiv 2022.04.24.489294; doi: https://doi.org/10.1101/2022.04.24.489294
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Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
Ryan J. Murphy, Gency Gunasingh, Nikolas K. Haass, Matthew J. Simpson
bioRxiv 2022.04.24.489294; doi: https://doi.org/10.1101/2022.04.24.489294

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