ArticleBMC systems biology2008
Essential operating principles for tumor spheroid growth.
Article in BMC systems biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Insights into spheroid formation: interaction of ovarian cancer cells with macrophage populations in the tumor microenvironment.Journal of translational medicine · 2025Article
- Energy Metabolism Behavior and Response to Microenvironmental Factors of the Experimental Cancer Cell Models Differ from that of Actual Human Tumors.Mini reviews in medicinal chemistry · 2025Review
- Nanoparticle-mediated cancer cell therapy: basic science to clinical applications.Cancer metastasis reviews · 2023Review
- A Bayesian approach to estimate the diffusion coefficient of Rhodamine 6G in breast cancer spheroids.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- A checkpoint-oriented cell cycle simulation model.Cell cycle (Georgetown, Tex.) · 2019Article
- Formation of cell spheroids using Standing Surface Acoustic Wave (SSAW).International journal of bioprinting · 2018Article
- Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success.Annals of biomedical engineering · 2016Review
- An agent-based modeling framework linking inflammation and cancer using evolutionary principles: description of a generative hierarchy for the hallmarks of cancer and developing a bridge between mechanism and epidemiological data.Mathematical biosciences · 2015Article
- Introduction of a Framework for Dynamic Knowledge Representation of the Control Structure of Transplant Immunology: Employing the Power of Abstraction with a Solid Organ Transplant Agent-Based Model.Frontiers in immunology · 2015Article
- Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.Journal of pharmacokinetics and pharmacodynamics · 2014Article
- Investigation of inflammation and tissue patterning in the gut using a Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT).PLoS computational biology · 2014Article
- Examining the pathogenesis of breast cancer using a novel agent-based model of mammary ductal epithelium dynamics.PloS one · 2013Article
- Modeling drug- and chemical-induced hepatotoxicity with systems biology approaches.Frontiers in physiology · 2012Article
- Modeling formalisms in Systems Biology.AMB Express · 2011Article
- Relational grounding facilitates development of scientifically useful multiscale models.Theoretical biology & medical modelling · 2011Review
- Self-organization of developing embryo using scale-invariant approach.Theoretical biology & medical modelling · 2011Article
- MDCK cystogenesis driven by cell stabilization within computational analogues.PLoS computational biology · 2011Article
- Emergent properties of tumor microenvironment in a real-life model of multicell tumor spheroids.PloS one · 2010Article
- Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms.BMC systems biology · 2010Article
- A computational approach to resolve cell level contributions to early glandular epithelial cancer progression.BMC systems biology · 2009Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOur objective was to discover in silico axioms that are plausible representations of the operating principles realized during characteristic growth of EMT6/Ro mouse mammary tumor spheroids in culture. To reach that objective we engineered and iteratively falsified an agent-based analogue of EMT6 spheroid growth. EMT6 spheroids display consistent and predictable growth characteristics, implying that individual cell behaviors are tightly controlled and regulated. An approach to understanding how individual cell behaviors contribute to system behaviors is to discover a set of principles that enable abstract agents to exhibit closely analogous behaviors using only information available in an agent's immediate environment. We listed key attributes of EMT6 spheroid growth, which became our behavioral targets. Included were the development of a necrotic core surrounded by quiescent and proliferating cells, and growth data at two distinct levels of nutrient.
resultsWe then created an analogue made up of quasi-autonomous software agents and an abstract environment in which they could operate. The system was designed so that upon execution it could mimic EMT6 cells forming spheroids in culture. Each agent used an identical set of axiomatic operating principles. In sequence, we used the list of targeted attributes to falsify and revise these axioms, until the analogue exhibited behaviors and attributes that were within prespecified ranges of those targeted, thereby achieving a level of validation.
conclusionThe finalized analogue required nine axioms. We posit that the validated analogue's operating principles are reasonable representations of those utilized by EMT6/Ro cells during tumor spheroid development.
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