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Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis.

ABSTRACT: Angiogenesis, the growth of capillaries from pre-existing ones, plays a key role in cancer progression. Tumours release tumour angiogenic factors (TAFs) into the extracellular matrix (ECM) that trigger angiogenesis once they reach the vasculature. The neovasculature provides nutrients and oxygen to the tumour. In the ECM, the interstitial fluid moves driven by pressure differences and may affect the distribution of tumour TAFs, and, in turn, tumour vascularization. In this work, we propose a hybrid mathematical model to investigate the influence of fluid flow in tumour angiogenesis. Our model shows the impact of interstitial flow in a time-evolving capillary network using a continuous approach. The flow model is coupled to a model of angiogenesis that includes tip endothelial cells, filopodia, capillaries and TAFs. The TAF transport equation considers not only diffusive mechanisms but also the convective transport produced by interstitial flow. Our simulations predict a significant alteration of the new vascular networks, which tend to grow more prominently against the flow. The model suggests that interstitial flow may produce increased tumour malignancies and hindered treatments.

SUBMITTER: Vilanova G

PROVIDER: S-EPMC6170778 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis.

Vilanova Guillermo G Burés Miguel M Colominas Ignasi I Gomez Hector H

Journal of the Royal Society, Interface 20180901 146

Angiogenesis, the growth of capillaries from pre-existing ones, plays a key role in cancer progression. Tumours release tumour angiogenic factors (TAFs) into the extracellular matrix (ECM) that trigger angiogenesis once they reach the vasculature. The neovasculature provides nutrients and oxygen to the tumour. In the ECM, the interstitial fluid moves driven by pressure differences and may affect the distribution of tumour TAFs, and, in turn, tumour vascularization. In this work, we propose a hyb ...[more]

PMID: 30185542

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Project description:Foot orthoses are prescribed to reduce forefoot plantar pressures and pain in people with rheumatoid arthritis. Computational modelling can assess how the orthoses affect internal tissue stresses, but previous studies have focused on a single healthy individual. This study aimed to ascertain whether simplified forefoot models would produce differing biomechanical predictions at the orthotic interface between people with rheumatoid arthritis of varying severity, and in comparison to a healthy control. The forefoot models were developed from magnetic resonance data of 13 participants with rheumatoid arthritis and one healthy individual. Measurements of bony morphology and soft tissue thickness were taken to assess deformity. These were compared to model predictions (99th% shear strain and plantar pressure, max. pressure gradient, volume of soft tissue over 10% shear strain), alongside clinical data including body mass index and Leeds Foot Impact Scale-Impairment/Footwear score (LFIS-IF). The predicted pressure and shear strain for the healthy participant fell at the lower end of the rheumatoid models' range. Medial first metatarsal head curvature moderately correlated to all model predicted outcomes (0.529 < r < 0.574, 0.040 < p < 0.063). BMI strongly correlated to all model predictions except pressure gradients (0.600 < r < 0.652, p < 0.05). There were no apparent relationships between model predictions and instances of bursae, erosion and synovial hypertrophy or LFIS-IF score. The forefoot models produced differing biomechanical predictions between a healthy individual and participants with rheumatoid arthritis, and between individuals with rheumatoid arthritis. Models capable of predicting subject specific biomechanical orthotic interactions could be used in the future to inform more personalised devices to protect skin and soft tissue health. While the model results did not clearly correlate with all clinical measures, there was a wide range in model predictions and morphological measures across the participants. Thus, the need for assessment of foot orthoses across a population, rather than for one individual, is clear.

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Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis.

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Computational modelling suggests complex interactions between interstitial flow and tumour angiogenesis.

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