Vilanova Guillermo, Colominas Ignasi, Gomez Hector
Departamento de Métodos Matemáticos e de Representación, Grupo de Métodos Numéricos en Ingeniería-Universidade da Coruña, Campus de Elviña, 15071 A Coruña, Spain
Departamento de Métodos Matemáticos e de Representación, Grupo de Métodos Numéricos en Ingeniería-Universidade da Coruña, Campus de Elviña, 15071 A Coruña, Spain.
J R Soc Interface. 2017 Jan;14(126). doi: 10.1098/rsif.2016.0918.
Cancerous tumours have the ability to recruit new blood vessels through a process called angiogenesis. By stimulating vascular growth, tumours get connected to the circulatory system, receive nutrients and open a way to colonize distant organs. Tumour-induced vascular networks become unstable in the absence of tumour angiogenic factors (TAFs). They may undergo alternating stages of growth, regression and regrowth. Following a phase-field methodology, we propose a model of tumour angiogenesis that reproduces the aforementioned features and highlights the importance of vascular regression and regrowth. In contrast with previous theories which focus on vessel remodelling due to the absence of flow, we model an alternative regression mechanism based on the dependency of tumour-induced vascular networks on TAFs. The model captures capillaries at full scale, the plastic dynamics of tumour-induced vessel networks at long time scales, and shows the key role played by filopodia during angiogenesis. The predictions of our model are in agreement with in vivo experiments and may prove useful for the design of antiangiogenic therapies.
癌性肿瘤能够通过一个名为血管生成的过程来招募新的血管。通过刺激血管生长，肿瘤与循环系统相连，获取营养并开辟一条向远处器官转移的途径。在没有肿瘤血管生成因子（TAFs）的情况下，肿瘤诱导的血管网络会变得不稳定。它们可能会经历生长、消退和再生长的交替阶段。遵循相场方法，我们提出了一个肿瘤血管生成模型，该模型再现了上述特征，并突出了血管消退和再生长的重要性。与以往侧重于因无血流而导致血管重塑的理论不同，我们基于肿瘤诱导的血管网络对TAFs的依赖性，建立了一种替代性的消退机制模型。该模型全面捕捉了毛细血管，展现了肿瘤诱导血管网络在长时间尺度上的可塑性动态，并显示了丝状伪足在血管生成过程中所起的关键作用。我们模型的预测结果与体内实验一致，可能对抗血管生成疗法的设计有用。
