title: A Validated Multiscale In-Silico Model for Mechano-sensitive Tumour Angiogenesis and Growth.
abstract: Vascularisation is a key feature of cancer growth, invasion and metastasis. To better understand the governing biophysical processes and their relative importance, it is instructive to develop physiologically representative mathematical models with which to compare to experimental data. Previous studies have successfully applied this approach to test the effect of various biochemical factors on tumour growth and angiogenesis. However, these models do not account for the experimentally observed dependency of angiogenic network evolution on growth-induced solid stresses. This work introduces two novel features: the effects of hapto- and mechanotaxis on vessel sprouting, and mechano-sensitive dynamic vascular remodelling. The proposed three-dimensional, multiscale, in-silico model of dynamically coupled angiogenic tumour growth is specified to in-vivo and in-vitro data, chosen, where possible, to provide a physiologically consistent description. The model is then validated against in-vivo data from murine mammary carcinomas, with particular focus placed on identifying the influence of mechanical factors. Crucially, we find that it is necessary to include hapto- and mechanotaxis to recapitulate observed time-varying spatial distributions of angiogenic vasculature.
authors.affiliation: University College London, Centre for Medical Image Computing, Department of Medical Physics & Biomedical Engineering, London, United Kingdom.
authors.forename: Vasileios
authors.identifier: 0000-0002-4102-2084
authors.initials: V
authors.lastname: Vavourakis
authors.affiliation: University College London, Centre for Medical Image Computing, Department of Medical Physics & Biomedical Engineering, London, United Kingdom.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Wijeratne
authors.affiliation: University College London, Department of Mechanical Engineering, London, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shipley
authors.affiliation: University College London, Department of Surgery, London, United Kingdom.
authors.forename: Marilena
authors.initials: M
authors.lastname: Loizidou
authors.affiliation: University of Cyprus, Department of Mechanical & Manufacturing Engineering, Nicosia, Cyprus.
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Stylianopoulos
authors.affiliation: University College London, Centre for Medical Image Computing, Department of Medical Physics & Biomedical Engineering, London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hawkes
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D049109:Cell Proliferation; D003198:Computer Simulation; D006801:Humans; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D033081:Shear Strength; D013314:Stress, Mechanical; D059016:Tumor Microenvironment / Q000502:physiology