Skip to content

Research at St Andrews

The effect of interstitial pressure on tumor growth: Coupling with the blood and lymphatic vascular systems

Research output: Contribution to journalArticle

Author(s)

M. Wu, H.B. Frieboes, S.R. McDougall, Mark A.J. Chaplain, Vittorio Cristini, J. Lowengrub

School/Research organisations

Abstract

The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform distribution of oxygen, solid tumor pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the interstitial fluid. © 2012 Elsevier Ltd.
Close

Details

Original languageEnglish
Pages (from-to)131-151
Number of pages21
JournalJournal of Theoretical Biology
Volume320
DOIs
Publication statusPublished - 7 Mar 2013

    Research areas

  • Vascular growth, Angiogenesis, Microenvironmental transport barriers, interstitual fluid flow

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Learning-induced switching costs in a parasitoid can maintain diversity of host aphid phenotypes although biocontrol is destabilized under abiotic stress

    Preedy, K., Chaplain, M. A. J., Leybourne, D., Marion, G. & Karley, A., 30 Mar 2020, In : Journal of Animal Ecology. Early View

    Research output: Contribution to journalArticle

  2. Bridging the gap between individual-based and continuum models of growing cell populations

    Chaplain, M. A. J., Lorenzi, T. & Macfarlane, F. R., Jan 2020, In : Journal of Mathematical Biology. 80, 1-2, p. 343-371

    Research output: Contribution to journalArticle

  3. Discrete and continuum phenotype-structured models for the evolution of cancer cell populations under chemotherapy

    Stace, R. E. A., Stiehl, T., Chaplain, M. A. J., Marciniak-Czochra, A. & Lorenzi, T., 2020, In : Mathematical Modelling of Natural Phenomena. 15, 22 p., 14.

    Research output: Contribution to journalArticle

  4. Quantitative predictive modelling approaches to understanding rheumatoid arthritis: a brief review

    Macfarlane, F. R., Chaplain, M. A. J. & Eftimie, R., 27 Dec 2019, In : Cells. 9, 1, 26 p., 74.

    Research output: Contribution to journalReview article

Related by journal

  1. Consistency and identifiability of the polymorphism-aware phylogenetic models

    Borges, R. & Kosiol, C., 7 Feb 2020, In : Journal of Theoretical Biology. 486, p. 1-6 6 p., 110074.

    Research output: Contribution to journalArticle

  2. A theory for investment across defences triggered at different stages of a predator-prey encounter

    Wang, L., Ruxton, G. D., Cornell, S. J., Speed, M. P. & Broom, M., 21 Jul 2019, In : Journal of Theoretical Biology. 473, p. 9-19 11 p.

    Research output: Contribution to journalArticle

  3. Spatial-stochastic modelling of synthetic gene regulatory networks

    Macnamara, C. K., Mitchell, E. & Chaplain, M. A. J., 10 Feb 2019, In : Journal of Theoretical Biology. In press

    Research output: Contribution to journalArticle

  4. Approximate Bayesian computation reveals the importance of repeated measurements for parameterising cell-based models of growing tissues

    Kursawe, J., Baker, R. E. & Fletcher, A. G., 14 Apr 2018, In : Journal of Theoretical Biology. 443, p. 66-81 16 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Journal of Theoretical Biology (Journal)

    Mark Andrew Joseph Chaplain (Editor)

    10 Apr 2017 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

ID: 206440355

Top