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

Natasha K. Martin, Eamonn A. Gaffney, Robert A. Gatenby, Philip K. Maini

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)461-470
Number of pages10
JournalJournal of Theoretical Biology
Issue number3
StatePublished - Dec 2010
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-C1-013-04
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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