Biomechanics and Modeling in Mechanobiology

, Volume 18, Issue 4, pp 1047–1078 | Cite as

Enhanced cancer cell invasion caused by fibroblasts when fluid flow is present

  • Jone Urdal
  • Jahn Otto Waldeland
  • Steinar EvjeEmail author


It has been demonstrated that interstitial fluid (IF) flow can play a crucial role in tumor cell progression. Swartz and collaborators (Cancer Cell 11: 526–538, Shields et al. 2007) demonstrated that cells that secrete the lymphoid homing chemokines CCL21/CCL19 and express their receptor CCR7 could use flow to bias the secreted chemokine, causing pericellular gradients that stimulate cells to migrate in the direction of the flow. In a further work by Shieh et al. (Cancer Res 71: 790–800, 2011), a synergetic enhancement of tumor cell invasion caused by interaction between tumor cells and fibroblasts in the presence of fluid flow was reported. In the present work, we extend a previous proposed cell-fluid mathematical model for autologous chemotaxis (Chem Eng Sci 191: 268–287, Waldeland and Evje 2018) to also include fibroblasts. This results in a cell-fibroblast-fluid model. Motivated by the experimental findings by Shieh et al, the momentum balance equation for the fibroblasts involves (1) a stress term that accounts for chemotaxis in the direction of positive gradients in secreted growth factor TGF-\(\beta \); (2) a fibroblast–ECM interaction term; (3) a cancer cell–fibroblast interaction term. Imposing reasonable simplifying assumptions, we derive an explicit expression for the cancer cell velocity \({\mathbf {u}}_{{\mathrm{c}}}\) that reveals a balance between a fluid-generated stress term, a chemotactic-driven migration term (autologous chemotaxis), and a new term that accounts for the possible mechanical interaction between fibroblasts and cancer cells. Similarly, the model provides an expression for the fibroblast velocity \({\mathbf {u}}_{{\mathrm{f}}}\) as well as the IF velocity \({\mathbf {u}}_{{\mathrm{w}}}\). The three-phase model is then used for comparison of the simulated output with experimental results to elucidate some of the possible mechanism(s) behind the reported fibroblast-enhanced tumor cell invasion.


Cell migration Fibroblast Multiphase flow Interstitial fluid Interstitial fluid pressure Autologous chemotaxis Chemokine Protease Growth factor 



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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jone Urdal
    • 1
  • Jahn Otto Waldeland
    • 1
  • Steinar Evje
    • 1
    Email author
  1. 1.University of StavangerStavangerNorway

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