Three-dimensional multispecies nonlinear tumor growth-II: Tumor invasion and angiogenesis.
Three-dimensional multispecies nonlinear tumor growth-II: Tumor invasion and angiogenesis.
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DOI：
10.1016/j.jtbi.2010.02.036
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发表时间：
2010-06-21
影响因子：
2
通讯作者：
Cristini, Vittorio
中科院分区：
文献类型：
--
作者：
Frieboes, Hermann B.;Jin, Fang;Chuang, Yao-Li;Wise, Steven M.;Lowengrub, John S.;Cristini, Vittorio
我们扩展了2003年建立的扩散界面模型来研究肿瘤的三维非线性生长。扩展包括通过连续扩散界面方法跟踪多个活细胞种群，通过血管生成的离散肿瘤血管的发生和老化，以及使用连续-离散混合方法结合单个细胞运动。我们研究疾病进展作为细胞尺度参数的函数，如增殖和氧/营养摄取速率。我们发现，由氧、细胞营养物质和代谢物的不均匀分布以及影响细胞尺度参数的表型变化引起的生理复杂的肿瘤微环境的异质性，可以定量地与肿瘤宏观尺度联系起来，作为促进形态不稳定的机制。这种不稳定性导致肿瘤通过周围健康组织的浸润而侵袭。如本研究所述，采用基于生物学的多尺度方法的模型可以帮助定量地将肿瘤微环境异质性的关键效应与临床观察到的肿瘤生长和侵袭联系起来。利用患者肿瘤特异性参数值，该方法可以为表征复杂的体内肿瘤生理特征和临床反应提供预测工具，从而改善治疗方式和预后。
We extend the diffuse interface model developed in to study nonlinear tumor growth in 3D. Extensions include the tracking of multiple viable cell species populations through a continuum diffuse-interface approach, onset and aging of discrete tumor vessels through angiogenesis, and incorporation of individual cell movement using a hybrid continuum-discrete approach. We investigate disease progression as a function of cellular-scale parameters such as proliferation and oxygen/nutrient uptake rates. We find that heterogeneity in the physiologically complex tumor microenvironment, caused by non-uniform distribution of oxygen, cell nutrients, and metabolites, as well as phenotypic changes affecting cellular-scale parameters, can be quantitatively linked to the tumor macro-scale as a mechanism that promotes morphological instability. This instability leads to invasion through tumor infiltration of surrounding healthy tissue. Models that employ a biologically-founded, multiscale approach, as illustrated in this work, could help to quantitatively link the critical effect of heterogeneity in the tumor microenvironment with clinically observed tumor growth and invasion. Using patient tumor-specific parameter values, this approach may provide a predictive tool to characterize the complex in vivo tumor physiological characteristics and clinical response, and thus lead to improved treatment modalities and prognosis.
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影响因子：
2
作者：
Bartha, K.;Rieger, H.
通讯作者：
Rieger, H.
影响因子：
2
作者：
Armstrong, Nicola J.;Painter, Kevin J.;Sherratt, Jonathan A.
通讯作者：
Sherratt, Jonathan A.
影响因子：
3.5
作者：
Breward, CJW;Byrne, HM;Lewis, CE
通讯作者：
Lewis, CE
影响因子：
11.5
作者：
Bello, L;Lucini, V;Bikfalvi, A
通讯作者：
Bikfalvi, A
影响因子：
3.5
作者：
Ambrosi, Davide;Preziosi, Luigi
通讯作者：
Preziosi, Luigi