×

Growth of tumours with stem cells: the effect of crowding and ageing of cells. (English) Zbl 07458623

Summary: Mathematical models for the growth of tumours in the presence of stem cells (CSCs) and differentiated tumour cells (CCs) are presented and discussed. The CSCs are assumed to be immortal and multipotent, i.e. capable of generating several possible lineages of CCs that may undergo ageing and apoptosis. Each CC is characterised by two indexes, related to the differentiation lineage and the class of age, respectively. Furthermore, the effect of crowding is taken into account, assuming that mitosis can be hindered by the presence of cells in the vicinity of the would-be mother cell. Two families of models are proposed. First, models based on cellular automata are considered, whose evolution is governed by stochastic rules. Then, by averaging over the cells with the same pair of indexes, we obtain a deterministic model that consists of a system of Ordinary Differential Equations (ODEs) whose unknown functions are the fractions of the cells in each lineage and the class of age. The system presents a basic novelty with respect to the other compartmental models proposed in the literature as it cannot be solved hierarchically because of the presence of the crowding effect. Numerical simulations based on the two families of models give the same qualitative results and, in particular, they evidentiate the occurrence of the tumour paradox: an increased mortality of the CCs may induce a faster growth of the tumour. A final section of the paper is devoted to the case in which the age distribution of the CCs is continuous and not discrete. In this case, an interesting mathematical problem is obtained that consists of one ODE for the fraction of CSCs and \(m\) first-order Partial Differential Equations (PDEs); one for each lineage of CCs.

MSC:

82-XX Statistical mechanics, structure of matter
Full Text: DOI

References:

[1] Tomasetti, C.; Li, L.; Vogelstein, B., Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention, Science, 355, 6331, 1330-1334 (2017)
[2] Tomasetti, C.; Vogelstein, B.; Parmigiani, G., Half or more of the somatic mutations in cancers of self-renewing tissues originate prior to tumor initiation, Proc. Natl. Acad. Sci., 110, 6, 1999-2004 (2013)
[3] Lapidot, T.; Sirard, C.; Vormoor, J.; Murdoch, B.; Hoang, T.; Caceres-Cortes, J.; Minden, M.; Paterson, B.; Caligiuri, M. A.; Dick, J. E., A cell initiating human acute myeloid leukaemia after transplantation into SCID mice, Nature, 367, 6464, 645 (1994)
[4] Reya, T.; Morrison, S. J.; Clarke, M. F.; Weissman, I. L., Stem cells, cancer, and cancer stem cells, Nature, 414, 6859, 105 (2001)
[5] Benítez, L.; Barberis, L.; Condat, C., Modeling tumorspheres reveals cancer stem cell niche building and plasticity, Physica A, 533, Article 121906 pp. (2019) · Zbl 07570006
[6] Al-Hajj, M.; Wicha, M. S.; Benito-Hernandez, A.; Morrison, S. J.; Clarke, M. F., Prospective identification of tumorigenic breast cancer cells, Proc. Natl. Acad. Sci., 100, 7, 3983-3988 (2003)
[7] Bellomo, N.; Li, N.; Maini, P. K., On the foundations of cancer modelling: selected topics, speculations, and perspectives, Math. Models Methods Appl. Sci., 18, 04, 593-646 (2008) · Zbl 1151.92014
[8] Huntly, B. J.; Gilliland, D. G., Cancer biology: summing up cancer stem cells, Nature, 435, 7046, 1169 (2005)
[9] Michor, F., Mathematical models of cancer stem cells, J. Clin. Oncol., 26, 17, 2854-2861 (2008)
[10] Visvader, J. E.; Lindeman, G. J., Cancer stem cells in solid tumours: accumulating evidence and unresolved questions, Nature Rev. Cancer, 8, 10, 755 (2008)
[11] Batlle, E.; Clevers, H., Cancer stem cells revisited, Nature Med., 23, 10, 1124 (2017)
[12] Clevers, H., The cancer stem cell: premises, promises and challenges, Nature Med., 17, 3, 313 (2011)
[13] Kakarala, M.; Wicha, M. S., Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy, J. Clin. Oncol., 26, 17, 2813-2820 (2008)
[14] Lathia, J. D.; Mack, S. C.; Mulkearns-Hubert, E. E.; Valentim, C. L.; Rich, J. N., Cancer stem cells in glioblastoma, Genes Dev., 29, 12, 1203-1217 (2015)
[15] Cancer Stem Cell News, J. D., Web site (2018), https://www.cancerstemcellnews.com/reviews/
[16] Bellomo, N.; Delitala, M., From the mathematical kinetic, and stochastic game theory to modelling mutations, onset, progression and immune competition of cancer cells, Phys. Life Rev., 5, 4, 183-206 (2008)
[17] Ganguly, R.; Puri, I., Mathematical model for the cancer stem cell hypothesis, Cell Prolif., 39, 1, 3-14 (2006)
[18] Weekes, S. L.; Barker, B.; Bober, S.; Cisneros, K.; Cline, J.; Thompson, A.; Hlatky, L.; Hahnfeldt, P.; Enderling, H., A multicompartment mathematical model of cancer stem cell-driven tumor growth dynamics, Bull. Math. Biol., 76, 7, 1762-1782 (2014) · Zbl 1300.92045
[19] Gentry, S. N.; Jackson, T. L., A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms, PLoS One, 8, 8, Article e71128 pp. (2013)
[20] Werner, B.; Scott, J. G.; Sottoriva, A.; Anderson, A. R.; Traulsen, A.; Altrock, P. M., The cancer stem cell fraction in hierarchically organized tumors can be estimated using mathematical modeling and patient-specific treatment trajectories, Cancer Res., canres-2069 (2016)
[21] Michor, F.; Hughes, T. P.; Iwasa, Y.; Branford, S.; Shah, N. P.; Sawyers, C. L.; Nowak, M. A., Dynamics of chronic myeloid leukaemia, Nature, 435, 7046, 1267 (2005)
[22] Marciniak-Czochra, A.; Stiehl, T.; Wagner, W., Modeling of replicative senescence in hematopoietic development, Aging (Albany NY), 1, 8, 723 (2009)
[23] Werner, B.; Dingli, D.; Lenaerts, T.; Pacheco, J. M.; Traulsen, A., Dynamics of mutant cells in hierarchical organized tissues, PLoS Comput. Biol., 7, 12, Article e1002290 pp. (2011)
[24] Kaveh, K.; Kohandel, M.; Sivaloganathan, S., Replicator dynamics of cancer stem cell: Selection in the presence of differentiation and plasticity, Math. Biosci., 272, 64-75 (2016) · Zbl 1369.92015
[25] Weiss, L. D.; Komarova, N. L.; Rodriguez-Brenes, I. A., Mathematical modeling of normal and cancer stem cells, Curr. Stem Cell Rep., 3, 3, 232-239 (2017)
[26] Anderson, A. R.; Weaver, A. M.; Cummings, P. T.; Quaranta, V., Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment, Cell, 127, 5, 905-915 (2006)
[27] Enderling, H.; Anderson, A. R.; Chaplain, M. A.; Beheshti, A.; Hlatky, L.; Hahnfeldt, P., Paradoxical dependencies of tumor dormancy and progression on basic cell kinetics, Cancer Res., 0008-5472 (2009)
[28] Meacci, L.; Primicerio, M., Mathematical models for tumours with cancer stem cells, Comput. Appl. Math., 6544-6559 (2018) · Zbl 1413.92010
[29] Monteagudo, Á.; Santos, J., Studying the capability of different cancer hallmarks to initiate tumor growth using a cellular automaton simulation. Application in a cancer stem cell context, Biosystems, 115, 46-58 (2014)
[30] Monteagudo, Á.; Santos, J., Treatment analysis in a cancer stem cell context using a tumor growth model based on cellular automata, PLoS One, 10, 7, Article e0132306 pp. (2015)
[31] Rocha, H.; Almeida, R.; Lima, E.; Resende, A.; Oden, J.; Yankeelov, T., A hybrid three-scale model of tumor growth, Math. Models Methods Appl. Sci., 28, 01, 61-93 (2018) · Zbl 1381.92051
[32] Poleszczuk, J.; Enderling, H., A high-performance cellular automaton model of tumor growth with dynamically growing domains, Appl. Math., 5, 1, 144 (2014)
[33] Poleszczuk, J.; Hahnfeldt, P.; Enderling, H., Evolution and phenotypic selection of cancer stem cells, PLoS Comput. Biol., 11, 3, Article e1004025 pp. (2015)
[34] Wodarz, D.; Komarova, N., Can loss of apoptosis protect against cancer?, Trends Genet., 23, 5, 232-237 (2007)
[35] Gurova, K. V.; Gudkov, A. V., Paradoxical role of apoptosis in tumor progression, J. Cell. Biochem., 88, 1, 128-137 (2003)
[36] Dingli, D.; Michor, F., Successful therapy must eradicate cancer stem cells, Stem Cells, 24, 12, 2603-2610 (2006)
[37] Betteridge, R.; Owen, M. R.; Byrne, H. M.; Alarcón, T.; Maini, P. K., The impact of cell crowding and active cell movement on vascular tumour growth, Netw. Heterog. Media, 1, 4, 515-535 (2006) · Zbl 1108.92022
[38] Hillen, T.; Enderling, H.; Hahnfeldt, P., The tumor growth paradox and immune system-mediated selection for cancer stem cells, Bull. Math. Biol., 75, 1, 161-184 (2013) · Zbl 1272.92026
[39] Borsi, I.; Fasano, A.; Primicerio, M.; Hillen, T., Mathematical properties of a non-local integro-PDE model for cancer stem cells, Math. Med. Biol., 34, 59-75 (2015) · Zbl 1400.92244
[40] Fasano, A.; Mancini, A.; Primicerio, M., Tumours with cancer stem cells: A PDE model, Math. Biosci., 272, 76-80 (2016) · Zbl 1371.92061
[41] Rodriguez-Brenes, I. A.; Komarova, N. L.; Wodarz, D., Evolutionary dynamics of feedback escape and the development of stem-cell-driven cancers, Proc. Natl. Acad. Sci., 108, 47, 18983-18988 (2011)
[42] Meacci, L.; de Oliveira Medeiros, D.; Buscaglia, G. C.; Primicerio, M., O paradoxo do crescimento tumoral através de um modelo 3D de autômatos celulares com células-tronco cancerígenas, C.Q.D. - Rev. Eletrônica Paul. Matemática, 14, 132-146 (2019), Edição Ermac
This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. In some cases that data have been complemented/enhanced by data from zbMATH Open. This attempts to reflect the references listed in the original paper as accurately as possible without claiming completeness or a perfect matching.