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Negative Feedback Regulation in Hierarchically Organized Tissues: Exploring the Dynamics of Tissue Regeneration and the Role of Feedback Escape in Tumor Development

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Book cover Mathematical Models of Tumor-Immune System Dynamics

Part of the book series: Springer Proceedings in Mathematics & Statistics ((PROMS,volume 107))

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Abstract

Hierarchically organized tissues are tightly regulated to maintain homeostasis under normal conditions and promote the rapid regeneration after injury. Negative feedback from the tissue itself plays an important role in establishing this control. In particular differentiated cells emit signals that down-regulate cell division and inhibit stem cell self-renewal. The mathematical analysis of how these two feedback mechanisms affect tissue regeneration and stability can provide important insights into the dynamics of tissue regulation. This topic is also important for the study of carcinogenesis, given that cancer development requires an escape from feedback control. Here we discuss various aspects of tissue regulation and the phenotypic evolutionary pathways that lead to escape from these feedback mechanisms. Furthermore, we discuss the various tumor growth patterns that arise through different feedback inactivations. Finally, by examining published clinical data we propose that the majority of tumor growth patterns found in the literature can be classified into five categories, which by themselves could reflect the different evolutionary events that drive tumor progression in different types of stem-cell-driven cancers.

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Acknowledgements

This work was funded by NIH grant R01 CA129286.

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Authors and Affiliations

  1. Department of Mathematics, University of California, Irvine, CA, 92697, USA

    Ignacio A. Rodriguez-Brenes & Natalia L. Komarova

  2. Department of Ecology and Evolution, University of California, Irvine, CA, 92697, USA

    Dominik Wodarz

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  1. Ignacio A. Rodriguez-Brenes
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  2. Natalia L. Komarova
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Correspondence to Dominik Wodarz .

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Editors and Affiliations

  1. Mathematics Department, The College of Saint Rose, Albany, New York, USA

    Amina Eladdadi

  2. School of Mathematics and Statistics, University of Sydney, Sydney, New South Wales, Australia

    Peter Kim

  3. Mathematical Sciences School, Queensland University of Technology, Brisbane, Queensland, Australia

    Dann Mallet

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Rodriguez-Brenes, I.A., Komarova, N.L., Wodarz, D. (2014). Negative Feedback Regulation in Hierarchically Organized Tissues: Exploring the Dynamics of Tissue Regeneration and the Role of Feedback Escape in Tumor Development. In: Eladdadi, A., Kim, P., Mallet, D. (eds) Mathematical Models of Tumor-Immune System Dynamics. Springer Proceedings in Mathematics & Statistics, vol 107. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1793-8_8

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