Tumour–stromal interactions in acid-mediated invasion: A mathematical model

Handle URI:
http://hdl.handle.net/10754/600088
Title:
Tumour–stromal interactions in acid-mediated invasion: A mathematical model
Authors:
Martin, Natasha K.; Gaffney, Eamonn A.; Gatenby, Robert A.; Maini, Philip K.
Abstract:
It is well established that the tumour microenvironment can both promote and suppress tumour growth and invasion, however, most mathematical models of invasion view the normal tissue as inhibiting tumour progression via immune modulation or spatial constraint. In particular, the production of acid by tumour cells and the subsequent creation of a low extracellular pH environment has been explored in several 'acid-mediated tumour invasion' models where the acidic environment facilitates normal cell death and permits tumour invasion. In this paper, we extend the acid-invasion model developed by Gatenby and Gawlinski (1996) to include both the competitive and cooperative interactions between tumour and normal cells, by incorporating the influence of extracellular matrix and protease production at the tumour-stroma interface. Our model predicts an optimal level of tumour acidity which produces both cell death and matrix degradation. Additionally, very aggressive tumours prevent protease production and matrix degradation by excessive normal cell destruction, leading to an acellular (but matrix filled) gap between the tumour and normal tissue, a feature seen in encapsulated tumours. These results suggest, counterintuitively, that increasing tumour acidity may, in some cases, prevent tumour invasion.
Citation:
Martin NK, Gaffney EA, Gatenby RA, Maini PK (2010) Tumour–stromal interactions in acid-mediated invasion: A mathematical model. Journal of Theoretical Biology 267: 461–470. Available: http://dx.doi.org/10.1016/j.jtbi.2010.08.028.
Publisher:
Elsevier BV
Journal:
Journal of Theoretical Biology
KAUST Grant Number:
KUK-C1-013-04
Issue Date:
Dec-2010
DOI:
10.1016/j.jtbi.2010.08.028
PubMed ID:
20816684
PubMed Central ID:
PMC3005191
Type:
Article
ISSN:
0022-5193
Sponsors:
Grant Support. NKM: This publication was funded by the National Cancer Institute, NIH grant U56CA113004. EAG: This publication is based on work supported in part by Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST). PKM: This work was partially supported by a Royal Society-Wolfson Research Merit Award. RAG and PKM: This work was partially supported by NIH grant 1U54CA143970-01.
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Full metadata record

DC FieldValue Language
dc.contributor.authorMartin, Natasha K.en
dc.contributor.authorGaffney, Eamonn A.en
dc.contributor.authorGatenby, Robert A.en
dc.contributor.authorMaini, Philip K.en
dc.date.accessioned2016-02-28T06:35:48Zen
dc.date.available2016-02-28T06:35:48Zen
dc.date.issued2010-12en
dc.identifier.citationMartin NK, Gaffney EA, Gatenby RA, Maini PK (2010) Tumour–stromal interactions in acid-mediated invasion: A mathematical model. Journal of Theoretical Biology 267: 461–470. Available: http://dx.doi.org/10.1016/j.jtbi.2010.08.028.en
dc.identifier.issn0022-5193en
dc.identifier.pmid20816684en
dc.identifier.doi10.1016/j.jtbi.2010.08.028en
dc.identifier.urihttp://hdl.handle.net/10754/600088en
dc.description.abstractIt is well established that the tumour microenvironment can both promote and suppress tumour growth and invasion, however, most mathematical models of invasion view the normal tissue as inhibiting tumour progression via immune modulation or spatial constraint. In particular, the production of acid by tumour cells and the subsequent creation of a low extracellular pH environment has been explored in several 'acid-mediated tumour invasion' models where the acidic environment facilitates normal cell death and permits tumour invasion. In this paper, we extend the acid-invasion model developed by Gatenby and Gawlinski (1996) to include both the competitive and cooperative interactions between tumour and normal cells, by incorporating the influence of extracellular matrix and protease production at the tumour-stroma interface. Our model predicts an optimal level of tumour acidity which produces both cell death and matrix degradation. Additionally, very aggressive tumours prevent protease production and matrix degradation by excessive normal cell destruction, leading to an acellular (but matrix filled) gap between the tumour and normal tissue, a feature seen in encapsulated tumours. These results suggest, counterintuitively, that increasing tumour acidity may, in some cases, prevent tumour invasion.en
dc.description.sponsorshipGrant Support. NKM: This publication was funded by the National Cancer Institute, NIH grant U56CA113004. EAG: This publication is based on work supported in part by Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST). PKM: This work was partially supported by a Royal Society-Wolfson Research Merit Award. RAG and PKM: This work was partially supported by NIH grant 1U54CA143970-01.en
dc.publisherElsevier BVen
dc.subjectAcidityen
dc.subjectCanceren
dc.subjectMicroenvironmenten
dc.subjectPHen
dc.subjectProteasesen
dc.subject.meshNeoplasm Invasivenessen
dc.subject.meshModels, Biologicalen
dc.titleTumour–stromal interactions in acid-mediated invasion: A mathematical modelen
dc.typeArticleen
dc.identifier.journalJournal of Theoretical Biologyen
dc.identifier.pmcidPMC3005191en
dc.contributor.institutionUniversity of Oxford, Oxford, United Kingdomen
dc.contributor.institutionUniversity of Bristol, Bristol, United Kingdomen
dc.contributor.institutionH. Lee Moffitt Cancer Center and Research Institute, Tampa, United Statesen
kaust.grant.numberKUK-C1-013-04en

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