Quantitative analysis of tumour spheroid structure.

Autor:	Browning AP; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.; ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Melbourne, Australia., Sharp JA; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.; ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Melbourne, Australia., Murphy RJ; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia., Gunasingh G; The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia., Lawson B; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.; ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Melbourne, Australia., Burrage K; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.; ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Melbourne, Australia.; Department of Computer Science, University of Oxford, Oxford, United Kingdom., Haass NK; The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia., Simpson M; School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Nov 29; Vol. 10. Date of Electronic Publication: 2021 Nov 29.
DOI:	10.7554/eLife.73020
Abstrakt:	Tumour spheroids are common in vitro experimental models of avascular tumour growth. Compared with traditional two-dimensional culture, tumour spheroids more closely mimic the avascular tumour microenvironment where spatial differences in nutrient availability strongly influence growth. We show that spheroids initiated using significantly different numbers of cells grow to similar limiting sizes, suggesting that avascular tumours have a limiting structure; in agreement with untested predictions of classical mathematical models of tumour spheroids. We develop a novel mathematical and statistical framework to study the structure of tumour spheroids seeded from cells transduced with fluorescent cell cycle indicators, enabling us to discriminate between arrested and cycling cells and identify an arrested region. Our analysis shows that transient spheroid structure is independent of initial spheroid size, and the limiting structure can be independent of seeding density. Standard experimental protocols compare spheroid size as a function of time; however, our analysis suggests that comparing spheroid structure as a function of overall size produces results that are relatively insensitive to variability in spheroid size. Our experimental observations are made using two melanoma cell lines, but our modelling framework applies across a wide range of spheroid culture conditions and cell lines. Competing Interests: AB, JS, RM, GG, BL, KB, NH, MS No competing interests declared (© 2021, Browning et al.)
Databáze:	MEDLINE
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