ArticleJournal of theoretical biology2012
Multispecies model of cell lineages and feedback control in solid tumors.
Article in Journal of theoretical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Virtual Clinical Trials of BMP4 Differentiation Therapy: Digital Twins to Aid Successful Glioblastoma Trial Design.bioRxiv : the preprint server for biology · 2025Article
- Spatial dynamics of feedback and feedforward regulation in cell lineages.PLoS computational biology · 2022Article
- Effect of feedback regulation on stem cell fractions in tissues and tumors: Understanding chemoresistance in cancer.Journal of theoretical biology · 2021Article
- Mathematical Models of Organoid Cultures.Frontiers in genetics · 2019Review
- A Visually Apparent and Quantifiable CT Imaging Feature Identifies Biophysical Subtypes of Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.Bulletin of mathematical biology · 2018Article
- Stability of Control Networks in Autonomous Homeostatic Regulation of Stem Cell Lineages.Bulletin of mathematical biology · 2018Article
- Modeling the dynamics of oligodendrocyte precursor cells and the genesis of gliomas.PLoS computational biology · 2018Article
- Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies model.Journal of theoretical biology · 2018Article
- Determining the control networks regulating stem cell lineages in colonic crypts.Journal of theoretical biology · 2017Article
- Radioresistance of the breast tumor is highly correlated to its level of cancer stem cell and its clinical implication for breast irradiation.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2017Article
- 3D Mathematical Modeling of Glioblastoma Suggests That Transdifferentiated Vascular Endothelial Cells Mediate Resistance to Current Standard-of-Care Therapy.Cancer research · 2017Article
- Multiscale Modeling of Glioblastoma Suggests that the Partial Disruption of Vessel/Cancer Stem Cell Crosstalk Can Promote Tumor Regression Without Increasing Invasiveness.IEEE transactions on bio-medical engineering · 2017Article
- Mathematical modeling links Wnt signaling to emergent patterns of metabolism in colon cancer.Molecular systems biology · 2017Article
- Optimal treatment and stochastic modeling of heterogeneous tumors.Biology direct · 2016Review
- Feedback Regulation in a Cancer Stem Cell Model can Cause an Allee Effect.Bulletin of mathematical biology · 2016Article
- Feedback, Lineages and Self-Organizing Morphogenesis.PLoS computational biology · 2016Article
- Cellular population dynamics control the robustness of the stem cell niche.Biology open · 2015Article
- A versatile mathematical work-flow to explore how Cancer Stem Cell fate influences tumor progression.BMC systems biology · 2015Article
- A multicompartment mathematical model of cancer stem cell-driven tumor growth dynamics.Bulletin of mathematical biology · 2014Article
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Authors and funding
4 authors.
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Abstract
We develop a multispecies continuum model to simulate the spatiotemporal dynamics of cell lineages in solid tumors. The model accounts for protein signaling factors produced by cells in lineages, and nutrients supplied by the microenvironment. Together, these regulate the rates of proliferation, self-renewal and differentiation of cells within the lineages, and control cell population sizes and distributions. Terminally differentiated cells release proteins (e.g., from the TGFβ superfamily) that feedback upon less differentiated cells in the lineage both to promote differentiation and decrease rates of proliferation (and self-renewal). Stem cells release a short-range factor that promotes self-renewal (e.g., representative of Wnt signaling factors), as well as a long-range inhibitor of this factor (e.g., representative of Wnt inhibitors such as Dkk and SFRPs). We find that the progression of the tumors and their response to treatment is controlled by the spatiotemporal dynamics of the signaling processes. The model predicts the development of spatiotemporal heterogeneous distributions of the feedback factors (Wnt, Dkk and TGFβ) and tumor cell populations with clusters of stem cells appearing at the tumor boundary, consistent with recent experiments. The nonlinear coupling between the heterogeneous expressions of growth factors and the heterogeneous distributions of cell populations at different lineage stages tends to create asymmetry in tumor shape that may sufficiently alter otherwise homeostatic feedback so as to favor escape from growth control. This occurs in a setting of invasive fingering, and enhanced aggressiveness after standard therapeutic interventions. We find, however, that combination therapy involving differentiation promoters and radiotherapy is very effective in eradicating such a tumor.
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