期刊论文详细信息
JOURNAL OF THEORETICAL BIOLOGY 卷:451
The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneitys
Article
Lorenzi, Tommaso1  Venkataraman, Chandrasekhar1  Lorz, Alexander2,3  Chaplain, Mark A. J.1 
[1] Univ St Andrews, Sch Math & Stat, St Andrews KY16 9SS, Fife, Scotland
[2] KAUST, CEMSE Div, Thuwal, Saudi Arabia
[3] UPMC Univ Paris 06, Sorbonne Univ, UMR 7598, Lab Jacques Louis Lions, Paris, France
关键词: Intratumour heterogeneity;    Phenotypic selection;    Mathematical oncology;    Partial differential equations;    Finite element methods;   
DOI  :  10.1016/j.jtbi.2018.05.002
来源: Elsevier
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【 摘 要 】

We present here a space-and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silica the role played by the spatial distribution of abiotic components of the tumour microenvironment in mediating phenotypic selection of cancer cells. Numerical simulations are performed both on the 3D geometry of an in silica multicellular tumour spheroid and on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography. The results obtained show that inhomogeneities in the spatial distribution of oxygen, currently observed in solid tumours, can promote the creation of distinct local niches and lead to the selection of different phenotypic variants within the same tumour. This process fosters the emergence of stable phenotypic heterogeneity and supports the presence of hypoxic cells resistant to cytotoxic therapy prior to treatment. Our theoretical results demonstrate the importance of integrating spatial data with ecological principles when evaluating the therapeutic response of solid tumours to cytotoxic therapy. (C) 2018 Elsevier Ltd. All rights reserved.

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