Evolutionary dynamics of glucose-deprived cancer cells: insights from experimentally informed mathematical modelling

被引:6
作者
Almeida, Luis [1 ]
Denis, Jerome Alexandre [2 ,3 ]
Ferrand, Nathalie [2 ]
Lorenzi, Tommaso [4 ]
Prunet, Antonin [1 ,2 ]
Sabbah, Michele [1 ]
Villa, Chiara [1 ]
机构
[1] Univ Paris, Sorbonne Univ, CNRS, Inria,Lab Jacques Louis Lions,UMR 7598, F-75005 Paris, France
[2] Sorbonne Univ, Inst Univ Cancerol, St Antoine Res Ctr CRSA, Canc Biol & Therapeut,INSERM,CNRS, F-75012 Paris, France
[3] Hop La Pitie Salpetriere, Dept Endocrinol & Oncol Biochem, F-75013 Paris, France
[4] Politecn Torino, Dept Math Sci G L Lagrange, Dipartimento Eccellenza 2018 2022, I-10129 Turin, Italy
基金
欧洲研究理事会;
关键词
metabolic reprogramming; evolutionary dynamics; phenotype-structured equations; MCT1; expression; breast cancer; mathematical modelling; LACTATE METABOLISM; SOLID TUMORS; HETEROGENEITY; MCT1;
D O I
10.1098/rsif.2023.0587
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Glucose is a primary energy source for cancer cells. Several lines of evidence support the idea that monocarboxylate transporters, such as MCT1, elicit metabolic reprogramming of cancer cells in glucose-poor environments, allowing them to re-use lactate, a by-product of glucose metabolism, as an alternative energy source with serious consequences for disease progression. We employ a synergistic experimental and mathematical modelling approach to explore the evolutionary processes at the root of cancer cell adaptation to glucose deprivation, with particular focus on the mechanisms underlying the increase in MCT1 expression observed in glucose-deprived aggressive cancer cells. Data from in vitro experiments on breast cancer cells are used to inform and calibrate a mathematical model that comprises a partial integro-differential equation for the dynamics of a population of cancer cells structured by the level of MCT1 expression. Analytical and numerical results of this model suggest that environment-induced changes in MCT1 expression mediated by lactate-associated signalling pathways enable a prompt adaptive response of glucose-deprived cancer cells, while fluctuations in MCT1 expression due to epigenetic changes create the substrate for environmental selection to act upon, speeding up the selective sweep underlying cancer cell adaptation to glucose deprivation, and may constitute a long-term bet-hedging mechanism.
引用
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页数:9
相关论文
共 49 条
[1]  
Almeida L., 2024, Figshare, DOI [10.6084/m9.figshare.c.6984358, DOI 10.6084/M9.FIGSHARE.C.6984358]
[2]   A Mathematical Dissection of the Adaptation of Cell Populations to Fluctuating Oxygen Levels [J].
Ardaseva, Aleksandra ;
Gatenby, Robert A. ;
Anderson, Alexander R. A. ;
Byrne, Helen M. ;
Maini, Philip K. ;
Lorenzi, Tommaso .
BULLETIN OF MATHEMATICAL BIOLOGY, 2020, 82 (06)
[3]   The metabolism of cancer cells during metastasis [J].
Bergers, Gabriele ;
Fendt, Sarah-Maria .
NATURE REVIEWS CANCER, 2021, 21 (03) :162-180
[4]   A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia [J].
Celora, Giulia L. ;
Bader, Samuel B. ;
Hammond, Ester M. ;
Maini, Philip K. ;
Pitt-Francis, Joe M. ;
Byrne, Helen M. .
JOURNAL OF THEORETICAL BIOLOGY, 2022, 545
[5]   Evolutionary dynamics of phenotype-structured populations: from individual-level mechanisms to population-level consequences [J].
Chisholm, Rebecca H. ;
Lorenzi, Tommaso ;
Desvillettes, Laurent ;
Hughes, Barry D. .
ZEITSCHRIFT FUR ANGEWANDTE MATHEMATIK UND PHYSIK, 2016, 67 (04)
[6]   Modeling the Dynamics of Heterogeneity of Solid Tumors in Response to Chemotherapy [J].
Cho, Heyrim ;
Levy, Doron .
BULLETIN OF MATHEMATICAL BIOLOGY, 2017, 79 (12) :2986-3012
[7]   Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects [J].
Corbet, Cyril ;
Bastien, Estelle ;
Draoui, Nihed ;
Doix, Bastien ;
Mignion, Lionel ;
Jordan, Benedicte F. ;
Marchand, Arnaud ;
Vanherck, Jean-Christophe ;
Chaltin, Patrick ;
Schakman, Olivier ;
Becker, Holger M. ;
Riant, Olivier ;
Feron, Olivier .
NATURE COMMUNICATIONS, 2018, 9
[8]   Targeting lactate metabolism for cancer therapeutics [J].
Doherty, Joanne R. ;
Cleveland, John L. .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (09) :3685-3692
[9]   Loss of WISP2/CCN5 in Estrogen-Dependent MCF7 Human Breast Cancer Cells Promotes a Stem-Like Cell Phenotype [J].
Ferrand, Nathalie ;
Gnanapragasam, Anne ;
Dorothee, Guillaume ;
Redeuilh, Gerard ;
Larsen, Annette K. ;
Sabbah, Michele .
PLOS ONE, 2014, 9 (02)
[10]   A Mathematical Study of the Influence of Hypoxia and Acidity on the Evolutionary Dynamics of Cancer [J].
Fiandaca, Giada ;
Delitala, Marcello ;
Lorenzi, Tommaso .
BULLETIN OF MATHEMATICAL BIOLOGY, 2021, 83 (07)