Gandolfi A, Franciscis S De, d'Onofrio A, Fasano A, Sinisgalli C
Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti" - CNR, Rome, Italy.
Instituto de Astrofísica de Andalucía (IAA-CSIC), Granada, Spain.
J Theor Biol. 2021 Mar 7;512:110526. doi: 10.1016/j.jtbi.2020.110526. Epub 2020 Oct 29.
This work considers the propagation of a tumor from the stage of a small avascular sphere in a host tissue and the progressive onset of a tumor neovasculature stimulated by a pro-angiogenic factor secreted by hypoxic cells. The way new vessels are formed involves cell sprouting from pre-existing vessels and following a trail via a chemotactic mechanism (CM). Namely, it is first proposed a detailed general family of models of the CM, based on a statistical mechanics approach. The key hypothesis is that the CM is composed by two components: i) the well-known bias induced by the angiogenic factor gradient; ii) the presence of stochastic changes of the velocity direction, thus giving rise to a diffusive component. Then, some further assumptions and simplifications are applied in order to derive a specific model to be used in the simulations. The tumor progression is favored by its acidic aggression towards the healthy cells. The model includes the evolution of many biological and chemical species. Numerical simulations show the onset of a traveling wave eventually replacing the host tissue with a fully vascularized tumor. The results of simulations agree with experimental measures of the vasculature density in tumors, even in the case of particularly hypoxic tumors.
这项工作考虑了肿瘤在宿主组织中从小的无血管球体阶段开始的扩散，以及由缺氧细胞分泌的促血管生成因子刺激引发的肿瘤新血管的逐渐形成。新血管形成的方式涉及从已有血管中长出细胞，并通过趋化机制（CM）沿着一条路径生长。具体而言，首先基于统计力学方法提出了一个详细的CM通用模型族。关键假设是CM由两个部分组成：i）血管生成因子梯度引起的众所周知的偏向；ii）速度方向的随机变化的存在，从而产生一个扩散分量。然后，应用一些进一步的假设和简化来推导一个用于模拟的特定模型。肿瘤对健康细胞的酸性侵袭有利于肿瘤进展。该模型包括许多生物和化学物质的演变。数值模拟显示出行波的出现，最终用完全血管化的肿瘤取代宿主组织。模拟结果与肿瘤中血管密度的实验测量结果一致，即使在特别缺氧的肿瘤情况下也是如此。
