The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity

Handle URI:
http://hdl.handle.net/10754/627825
Title:
The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity
Authors:
Lorenzi, Tommaso; Venkataraman, Chandrasekhar ( 0000-0003-4039-2056 ) ; Lorz, Alexander; Chaplain, Mark A.J. ( 0000-0001-5727-2160 )
Abstract:
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 silico 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 silico 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.
KAUST Department:
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Lorenzi T, Venkataraman C, Lorz A, Chaplain MAJ (2018) The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity. Journal of Theoretical Biology. Available: http://dx.doi.org/10.1016/j.jtbi.2018.05.002.
Publisher:
Elsevier BV
Journal:
Journal of Theoretical Biology
KAUST Grant Number:
BAS/1/1648-01-01; BAS/1/1648-01-02
Issue Date:
8-May-2018
DOI:
10.1016/j.jtbi.2018.05.002
Type:
Article
ISSN:
0022-5193
Sponsors:
The authors would like to thank Dana-Adriana Botesteanu for her helpful feedback and insightful comments and suggestions. CV wishes to acknowledge partial support from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642866. AL was supported by King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). MAJC gratefully acknowledge support of EPSRC grant no. EP/N014642/1.
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0022519318302273
Appears in Collections:
Articles; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorLorenzi, Tommasoen
dc.contributor.authorVenkataraman, Chandrasekharen
dc.contributor.authorLorz, Alexanderen
dc.contributor.authorChaplain, Mark A.J.en
dc.date.accessioned2018-05-10T08:56:43Z-
dc.date.available2018-05-10T08:56:43Z-
dc.date.issued2018-05-08en
dc.identifier.citationLorenzi T, Venkataraman C, Lorz A, Chaplain MAJ (2018) The role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneity. Journal of Theoretical Biology. Available: http://dx.doi.org/10.1016/j.jtbi.2018.05.002.en
dc.identifier.issn0022-5193en
dc.identifier.doi10.1016/j.jtbi.2018.05.002en
dc.identifier.urihttp://hdl.handle.net/10754/627825-
dc.description.abstractWe 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 silico 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 silico 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.en
dc.description.sponsorshipThe authors would like to thank Dana-Adriana Botesteanu for her helpful feedback and insightful comments and suggestions. CV wishes to acknowledge partial support from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642866. AL was supported by King Abdullah University of Science and Technology (KAUST) baseline and start-up funds (BAS/1/1648-01-01 and BAS/1/1648-01-02). MAJC gratefully acknowledge support of EPSRC grant no. EP/N014642/1.en
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0022519318302273en
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Journal of Theoretical Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Theoretical Biology, 8 May 2018. DOI: 10.1016/j.jtbi.2018.05.002. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectIntratumour heterogeneityen
dc.subjectPhenotypic selectionen
dc.subjectMathematical oncologyen
dc.subjectPartial differential equationsen
dc.subjectFinite element methodsen
dc.titleThe role of spatial variations of abiotic factors in mediating intratumour phenotypic heterogeneityen
dc.typeArticleen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalJournal of Theoretical Biologyen
dc.eprint.versionPost-printen
dc.contributor.institutionSchool of Mathematics and Statistics, University of St Andrews, St Andrews KY16 9SS, United Kingdomen
dc.contributor.institutionSorbonne Universités, UPMC Univ Paris 06, UMR 7598, Laboratoire Jacques-Louis Lions, Paris, Franceen
kaust.authorLorz, Alexanderen
kaust.grant.numberBAS/1/1648-01-01en
kaust.grant.numberBAS/1/1648-01-02en
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