Exploring cancer stem cell niche directed tumor growth

Sottoriva, Andrea; Sloot, Peter M. A.; Medema, Jan Paul; Vermeulen, Louis

doi:10.4161/cc.9.8.11198

Cited by 35 publications

(34 citation statements)

References 44 publications

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“…Dedifferentiation due to ‘niche’ specific factors was studied by Sottoriva et al [33], who, using an agent based model, reported findings similar to ours: that the microenvironment made no significant change to the overall tumour growth dynamics. Beyond this single spatial study, the concept of SC dedifferentiation is gaining more and more attention in conceptual theoretical treatments [34] and has been modelled with a deterministic ordinary differential equation system for a well-mixed population of cells [35].…”

Section: Discussionsupporting

confidence: 82%

Microenvironmental Variables Must Influence Intrinsic Phenotypic Parameters of Cancer Stem Cells to Affect Tumourigenicity

et al. 2014

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Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non-specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly affect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

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Section: Discussionsupporting

confidence: 82%

Microenvironmental Variables Must Influence Intrinsic Phenotypic Parameters of Cancer Stem Cells to Affect Tumourigenicity

et al. 2014

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“…Gerlee and co-workers [32] used mathematical modelling to investigate primary versus secondary seeding in a breast primary tumour. Sottoriva and co-workers have used modelling to study stem cell niche dynamics [33], tumour heterogeneity and invasion [34]. In several studies, Enderling and co-workers have modelled stem cell originated tumour growth [35][36][37][38].…”

Section: Introductionmentioning

confidence: 99%

An agent-based model of cancer stem cell initiated avascular tumour growth and metastasis: the effect of seeding frequency and location

Norton

Popel

2014

J. R. Soc. Interface.

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ResearchCite this article: Norton K-A, Popel AS. 2014 An agent-based model of cancer stem cell initiated avascular tumour growth and metastasis: the effect of seeding frequency and location. J. R. Soc. It is very important to understand the onset and growth pattern of breast primary tumours as well as their metastatic dissemination. In most cases, it is the metastatic disease that ultimately kills the patient. There is increasing evidence that cancer stem cells are closely linked to the progression of the metastatic tumour. Here, we investigate stem cell seeding to an avascular tumour site using an agent-based stochastic model of breast cancer metastatic seeding. The model includes several important cellular features such as stem cell symmetric and asymmetric division, migration, cellular quiescence, senescence, apoptosis and cell division cycles. It also includes external features such as stem cell seeding frequency and location. Using this model, we find that cell seeding rate and location are important features for tumour growth. We also define conditions in which the tumour growth exhibits decremented and exponential growth patterns. Overall, we find that seeding, senescence and division limit affect not only the number of stem cells, but also their spatial and temporal distribution.

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“…All these studies investigate the well-known mechanism of androgen-independent relapse and do not consider cell transdifferentiation as such. Also, differently from the mathematical approach followed in other types of tumors, for example, colonic crypt and colorectal cancer (26)(27)(28), in the case of prostate cancer the well-established theory of cancer stem cells, which assumes an asymmetrical cell division (29), has not been considered in the representation of tumor growth (1,30). In our model (A1-A3) according with the cancer stem cell theory, we assumed that LNCaP mitosis leads to the formation of both undifferentiated and differentiated cells.…”

Section: Formulation Of the Mathematical Modelmentioning

confidence: 99%

Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach

et al. 2015

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Prostate cancer is highly sensitive to hormone therapy because androgens are essential for prostate cancer cell growth. However, with the nearly invariable progression of this disease to androgen independence, endocrine therapy ultimately fails to control prostate cancer in most patients. Androgen-independent acquisition may involve neuroendocrine transdifferentiation, but there is little knowledge about this process, which is presently controversial. In this study, we investigated this question in a novel model of human androgen-dependent LNCaP cells cultured for long periods in hormone-deprived conditions. Strikingly, characterization of the neuroendocrine phenotype by transcriptomic, metabolomic, and other statistically integrated analyses showed how hormone-deprived LNCaP cells could transdifferentiate to a nonmalignant neuroendocrine phenotype. Notably, conditioned media from neuroendocrine-like cells affected LNCaP cell proliferation. Predictive in silico models illustrated how after an initial period, when LNCaP cell survival was compromised by an arising population of neuroendocrine-like cells, a sudden trend reversal occurred in which the neuroendocrine-like cells functioned to sustain the remaining androgen-dependent LNCaP cells. Our findings provide direct biologic and molecular support for the concept that neuroendocrine transdifferentiation in prostate cancer cell populations influences the progression to androgen independence. Cancer Res; 75(15); 2975-86. Ó2015 AACR.

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Exploring cancer stem cell niche directed tumor growth

Cited by 35 publications

References 44 publications

Microenvironmental Variables Must Influence Intrinsic Phenotypic Parameters of Cancer Stem Cells to Affect Tumourigenicity

Microenvironmental Variables Must Influence Intrinsic Phenotypic Parameters of Cancer Stem Cells to Affect Tumourigenicity

An agent-based model of cancer stem cell initiated avascular tumour growth and metastasis: the effect of seeding frequency and location

Neuroendocrine Transdifferentiation in Human Prostate Cancer Cells: An Integrated Approach

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