No Cover Image

Journal article 549 views 91 downloads

Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion

KEVIN SPINICCI, Gibin Powathil Orcid Logo, Angélique Stéphanou

Bulletin of Mathematical Biology, Volume: 87, Issue: 2

Swansea University Authors: KEVIN SPINICCI, Gibin Powathil Orcid Logo

  • 68592.VoR.pdf

    PDF | Version of Record

    © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License.

    Download (2.38MB)

Check full text

DOI (Published version): 10.1007/s11538-024-01391-0

Abstract

The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and i...

Full description

Published in: Bulletin of Mathematical Biology
ISSN: 0092-8240 1522-9602
Published: Springer Science and Business Media LLC 2025
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa68592
first_indexed 2025-01-09T20:33:55Z
last_indexed 2025-01-29T20:24:16Z
id cronfa68592
recordtype SURis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2025-01-29T13:49:52.5413167</datestamp><bib-version>v2</bib-version><id>68592</id><entry>2024-12-18</entry><title>Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion</title><swanseaauthors><author><sid>a1c53ecd60a1e5c342e2bdaa93461c12</sid><firstname>KEVIN</firstname><surname>SPINICCI</surname><name>KEVIN SPINICCI</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>f23646a94239f673e2a43ebe7397aabd</sid><ORCID>0000-0002-8372-7349</ORCID><firstname>Gibin</firstname><surname>Powathil</surname><name>Gibin Powathil</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2024-12-18</date><abstract>The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies. Furthermore, increased cancer cell migration and invasion have been observed in hypoxic conditions. Interestingly, it has been revealed that the Hypoxia Inducible Factor (HIF) can not only impact the levels of metabolic genes but several collagen remodeling genes as well. The goal of this paper is to explore the impact of the HIF protein on both the tumour metabolism and the cancer cell migration with a focus on the Warburg effect and collagen remodelling processes. Therefore, we present an agent-based model (ABM) of tumour growth combining genetic regulations with metabolic and collagen-related processes involved in HIF pathways. Cancer cell migration is influenced by the extra-cellular collagen through a biphasic response dependant on collagen density. Results of the model showed that extra-cellular collagen within the tumour was mainly influenced by the local cellular density while collagen also influenced the shape of the tumour. In our simulations, proliferation was reduced with higher extra-cellular collagen levels or with lower oxygen levels but reached a maximum in the absence of cell-cell adhesion. Interestingly, combining lower levels of oxygen with higher levels of collagen further reduced the proliferation of the tumour. Since HIF impacts the metabolism and may affect the appearance of the Warburg Effect, we investigated whether different collagen conditions could lead to the adoption of the Warburg phenotype. We found that this was not the case, results suggested that adoption of the Warburg phenotype seemed mainly controlled by inhibition of oxidative metabolism by HIF combined with oscillations of oxygen.</abstract><type>Journal Article</type><journal>Bulletin of Mathematical Biology</journal><volume>87</volume><journalNumber>2</journalNumber><paginationStart/><paginationEnd/><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0092-8240</issnPrint><issnElectronic>1522-9602</issnElectronic><keywords>Hypoxia inducible factor; Cell migration; Warburg effect; Extra-cellular matrix; Agent-based model</keywords><publishedDay>3</publishedDay><publishedMonth>1</publishedMonth><publishedYear>2025</publishedYear><publishedDate>2025-01-03</publishedDate><doi>10.1007/s11538-024-01391-0</doi><url/><notes/><college>COLLEGE NANME</college><CollegeCode>COLLEGE CODE</CollegeCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders>This work is supported by the French National Research Agency in the framework of the &#x201C;Investissements d&#x2019;avenir&#x201D; program (ANR-15-IDEX-02). K&#xE9;vin Spinicci gratefully acknowledges the support of Swansea University Strategic Partnership Research Scholarship and the support of IDEX Universit&#xE9; Grenoble Alpes.</funders><projectreference/><lastEdited>2025-01-29T13:49:52.5413167</lastEdited><Created>2024-12-18T13:03:18.4890182</Created><path><level id="1">Faculty of Science and Engineering</level><level id="2">School of Mathematics and Computer Science - Mathematics</level></path><authors><author><firstname>KEVIN</firstname><surname>SPINICCI</surname><order>1</order></author><author><firstname>Gibin</firstname><surname>Powathil</surname><orcid>0000-0002-8372-7349</orcid><order>2</order></author><author><firstname>Ang&#xE9;lique</firstname><surname>St&#xE9;phanou</surname><order>3</order></author></authors><documents><document><filename>68592__33435__10752a9de64a4410b06f9194ebefe7a1.pdf</filename><originalFilename>68592.VoR.pdf</originalFilename><uploaded>2025-01-29T13:46:39.2712358</uploaded><type>Output</type><contentLength>2497458</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling 2025-01-29T13:49:52.5413167 v2 68592 2024-12-18 Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion a1c53ecd60a1e5c342e2bdaa93461c12 KEVIN SPINICCI KEVIN SPINICCI true false f23646a94239f673e2a43ebe7397aabd 0000-0002-8372-7349 Gibin Powathil Gibin Powathil true false 2024-12-18 The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies. Furthermore, increased cancer cell migration and invasion have been observed in hypoxic conditions. Interestingly, it has been revealed that the Hypoxia Inducible Factor (HIF) can not only impact the levels of metabolic genes but several collagen remodeling genes as well. The goal of this paper is to explore the impact of the HIF protein on both the tumour metabolism and the cancer cell migration with a focus on the Warburg effect and collagen remodelling processes. Therefore, we present an agent-based model (ABM) of tumour growth combining genetic regulations with metabolic and collagen-related processes involved in HIF pathways. Cancer cell migration is influenced by the extra-cellular collagen through a biphasic response dependant on collagen density. Results of the model showed that extra-cellular collagen within the tumour was mainly influenced by the local cellular density while collagen also influenced the shape of the tumour. In our simulations, proliferation was reduced with higher extra-cellular collagen levels or with lower oxygen levels but reached a maximum in the absence of cell-cell adhesion. Interestingly, combining lower levels of oxygen with higher levels of collagen further reduced the proliferation of the tumour. Since HIF impacts the metabolism and may affect the appearance of the Warburg Effect, we investigated whether different collagen conditions could lead to the adoption of the Warburg phenotype. We found that this was not the case, results suggested that adoption of the Warburg phenotype seemed mainly controlled by inhibition of oxidative metabolism by HIF combined with oscillations of oxygen. Journal Article Bulletin of Mathematical Biology 87 2 Springer Science and Business Media LLC 0092-8240 1522-9602 Hypoxia inducible factor; Cell migration; Warburg effect; Extra-cellular matrix; Agent-based model 3 1 2025 2025-01-03 10.1007/s11538-024-01391-0 COLLEGE NANME COLLEGE CODE Swansea University SU Library paid the OA fee (TA Institutional Deal) This work is supported by the French National Research Agency in the framework of the “Investissements d’avenir” program (ANR-15-IDEX-02). Kévin Spinicci gratefully acknowledges the support of Swansea University Strategic Partnership Research Scholarship and the support of IDEX Université Grenoble Alpes. 2025-01-29T13:49:52.5413167 2024-12-18T13:03:18.4890182 Faculty of Science and Engineering School of Mathematics and Computer Science - Mathematics KEVIN SPINICCI 1 Gibin Powathil 0000-0002-8372-7349 2 Angélique Stéphanou 3 68592__33435__10752a9de64a4410b06f9194ebefe7a1.pdf 68592.VoR.pdf 2025-01-29T13:46:39.2712358 Output 2497458 application/pdf Version of Record true © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/
title Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
spellingShingle Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
KEVIN SPINICCI
Gibin Powathil
title_short Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
title_full Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
title_fullStr Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
title_full_unstemmed Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
title_sort Modelling the Impact of HIF on Metabolism and the Extracellular Matrix: Consequences for Tumour Growth and Invasion
author_id_str_mv a1c53ecd60a1e5c342e2bdaa93461c12
f23646a94239f673e2a43ebe7397aabd
author_id_fullname_str_mv a1c53ecd60a1e5c342e2bdaa93461c12_***_KEVIN SPINICCI
f23646a94239f673e2a43ebe7397aabd_***_Gibin Powathil
author KEVIN SPINICCI
Gibin Powathil
author2 KEVIN SPINICCI
Gibin Powathil
Angélique Stéphanou
format Journal article
container_title Bulletin of Mathematical Biology
container_volume 87
container_issue 2
publishDate 2025
institution Swansea University
issn 0092-8240
1522-9602
doi_str_mv 10.1007/s11538-024-01391-0
publisher Springer Science and Business Media LLC
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Mathematics and Computer Science - Mathematics{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Mathematics and Computer Science - Mathematics
document_store_str 1
active_str 0
description The extracellular matrix (ECM) is a complex structure involved in many biological processes with collagen being the most abundant protein. Density of collagen fibers in the matrix is a factor influencing cell motility and migration speed. In cancer, this affects the ability of cells to migrate and invade distant tissues which is relevant for designing new therapies. Furthermore, increased cancer cell migration and invasion have been observed in hypoxic conditions. Interestingly, it has been revealed that the Hypoxia Inducible Factor (HIF) can not only impact the levels of metabolic genes but several collagen remodeling genes as well. The goal of this paper is to explore the impact of the HIF protein on both the tumour metabolism and the cancer cell migration with a focus on the Warburg effect and collagen remodelling processes. Therefore, we present an agent-based model (ABM) of tumour growth combining genetic regulations with metabolic and collagen-related processes involved in HIF pathways. Cancer cell migration is influenced by the extra-cellular collagen through a biphasic response dependant on collagen density. Results of the model showed that extra-cellular collagen within the tumour was mainly influenced by the local cellular density while collagen also influenced the shape of the tumour. In our simulations, proliferation was reduced with higher extra-cellular collagen levels or with lower oxygen levels but reached a maximum in the absence of cell-cell adhesion. Interestingly, combining lower levels of oxygen with higher levels of collagen further reduced the proliferation of the tumour. Since HIF impacts the metabolism and may affect the appearance of the Warburg Effect, we investigated whether different collagen conditions could lead to the adoption of the Warburg phenotype. We found that this was not the case, results suggested that adoption of the Warburg phenotype seemed mainly controlled by inhibition of oxidative metabolism by HIF combined with oscillations of oxygen.
published_date 2025-01-03T05:25:53Z
_version_ 1851097720472731648
score 11.089407

Similar Items