Laboratori de Càlcul Numèric, Universitat Politècnica de Catalunya, Campus Nord, 08034 Barcelona, Spain
School of Mechanical Engineering, Purdue University, 585 Purdue Mall, West Lafayette, IN 47907, USA.
J R Soc Interface. 2018 Sep;15(146). doi: 10.1098/rsif.2018.0415.
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.
血管生成，即毛细血管从已有的血管中生长，在癌症进展中起着关键作用。肿瘤将肿瘤血管生成因子（TAFs）释放到细胞外基质（ECM）中，一旦到达脉管系统就会引发血管生成。新生血管为肿瘤提供营养和氧气。在 ECM 中，间质液在压力差的驱动下移动，可能会影响肿瘤 TAFs 的分布，进而影响肿瘤血管生成。在这项工作中，我们提出了一种混合数学模型来研究流体流动对肿瘤血管生成的影响。我们的模型使用连续方法展示了间质流在时变毛细血管网络中的影响。流动模型与血管生成模型耦合，其中包括尖端内皮细胞、丝状伪足、毛细血管和 TAFs。TAF 输运方程不仅考虑了扩散机制，还考虑了间质流产生的对流输运。我们的模拟预测了新的血管网络的显著变化，这些网络往往会更明显地沿着血流方向生长。该模型表明，间质流可能会导致肿瘤恶性程度增加和治疗受阻。
