Arshadi Soroosh, Pishevar Ahmadreza, Javanbakht Mahdi, Javanmard Shaghayegh Haghjooy
Department of Mechanical Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
Department of Mechanical Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
Math Biosci. 2025 Feb;380:109366. doi: 10.1016/j.mbs.2024.109366. Epub 2024 Dec 15.
In this paper, we propose a vascular tumor growth model that combines a phase-field tumor model with a phase-field angiogenesis model. By incorporating various tumor cell species, we capture the instabilities of the tumor in the presence of evolving neovasculature. The model not only considers different dynamics of tumor cell phase conversions, movement, and pressure effects but also provides a comprehensive representation of angiogenesis, encompassing chemotaxis of endothelial cells, sprouting, anastomoses, and blood flow in capillaries. This study evaluates the impact of chemotaxis on tumor cell movement in both avascular and vascular tumor growth scenarios. The results highlight the acceleration of tumor growth when angiogenesis is stimulated. Additionally, the investigation explores various initial distances of the tumor from neighboring vessels, revealing a critical threshold distance beyond which the angiogenesis factor fails to stimulate angiogenesis, resulting in the tumor maintaining a stable state. The integration of chemotaxis into the growth model induces instabilities, leading to increased nutrient availability and faster growth for the tumor. Furthermore, the study considers anti-angiogenesis therapy as an ideal approach, assuming complete inhibition of angiogenesis from the early stages. In this scenario, the tumor persists in a steady state, adhering to the avascular size limit in the absence of neovasculature. Conversely, when considering chemotaxis, anti-angiogenesis therapy loses efficiency, enabling unrestrained tumor growth towards neighboring vessels. This work sheds light on the intricate interplay among chemotaxis, angiogenesis, and anti-angiogenesis therapy in the context of vascular tumor growth, providing valuable insights for the development of targeted treatment strategies.
在本文中，我们提出了一种血管肿瘤生长模型，该模型将相场肿瘤模型与相场血管生成模型相结合。通过纳入各种肿瘤细胞类型，我们捕捉了在不断演变的新血管存在下肿瘤的不稳定性。该模型不仅考虑了肿瘤细胞相转换、运动和压力效应的不同动态，还提供了血管生成的全面表征，包括内皮细胞的趋化性、芽生、吻合以及毛细血管中的血流。本研究评估了趋化性在无血管和血管肿瘤生长情况下对肿瘤细胞运动的影响。结果突出了血管生成被刺激时肿瘤生长的加速。此外，该研究探讨了肿瘤与相邻血管的各种初始距离，揭示了一个临界阈值距离，超过该距离血管生成因子无法刺激血管生成，导致肿瘤维持稳定状态。将趋化性纳入生长模型会引发不稳定性，导致肿瘤的营养供应增加和生长加快。此外，该研究将抗血管生成疗法视为一种理想方法，假设从早期阶段就完全抑制血管生成。在这种情况下，肿瘤在无新血管的情况下维持在稳定状态，遵循无血管大小限制。相反，当考虑趋化性时，抗血管生成疗法失去效果，使肿瘤能够不受限制地向相邻血管生长。这项工作揭示了血管肿瘤生长背景下趋化性、血管生成和抗血管生成疗法之间的复杂相互作用，为靶向治疗策略的开发提供了有价值的见解。
