Tumor morphological evolution: directed migration and gain and loss of the self-metastatic phenotype
Tumor morphological evolution: directed migration and gain and loss of the self-metastatic phenotype
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DOI：
10.1186/1745-6150-5-23
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发表时间：
2010-04-20
期刊：
影响因子：
5.5
通讯作者：
Hahnfeldt, Philip
中科院分区：
文献类型：
--
作者：
Enderling, Heiko;Hlatky, Lynn;Hahnfeldt, Philip
背景：除了已知癌细胞形成的逐步遗传改变外，已知微环境深刻影响随后的肿瘤发展，形态和转移。侵袭性簇的形成一直被认为依赖于定向迁移和异质环境，这是一个从肿瘤-环境相互作用的复杂模型中得出的结论。与此同时，这些模型没有考虑到只有少数癌细胞可能具有干细胞能力的前景，而现在有大量证据支持这一前景。这证明了对显示特征性肿瘤生长表型的微环境要求的重要性。我们使用基于智能体的建模表明，在随机迁移下，定向迁移也可能实现肿瘤生长的一些定义特征，并讨论了一般因果确定的更广泛含义。结果：仅考虑由干细胞和承诺细胞组成的肿瘤的随机迁移特性，我们能够概括出侵袭性肿瘤生长的特征聚类特征，我们将这种特性归因于“自我转移”生长。当考虑趋化环境下定向迁移的额外影响时，我们发现当肿瘤远离源时，肿瘤的生长和浸润形态得到支持，但随着肿瘤向源收敛，肿瘤的生长和浸润形态逐渐受到抑制。结论：我们表明，侵入性聚类可以从基本的动力学假设中推导出来，这些假设在更复杂的模型中经常被忽视。虽然高阶机制，例如在趋化刺激下的定向迁移，可能导致集群生长形态，但根据我们的发现，将这种表型专属于这种或其他结构化微环境是不合适的，因为这些特征在同质环境中是可观察到的。此外，当肿瘤接近吸引源时，定向迁移将导致侵袭性表型的丧失。书评人：本文的书评人是Mark Little和Glen Webb。
Background: Aside from the stepwise genetic alterations known to underlie cancer cell creation, the microenvironment is known to profoundly influence subsequent tumor development, morphology and metastasis. Invasive cluster formation has been assumed to be dependent on directed migration and a heterogeneous environment - a conclusion derived from complex models of tumor-environment interaction. At the same time, these models have not included the prospect, now supported by a preponderance of evidence, that only a minority of cancer cells may have stem cell capacity. This proves to weigh heavily on the microenvironmental requirements for the display of characteristic tumor growth phenotypes. We show using agent-based modeling that some defining features of tumor growth ascribed to directed migration might also be realized under random migration, and discuss broader implications for cause-and-effect determination in general.Results: Considering only the properties of random migration in tumors composed of stem cells and committed cells, we are able to recapitulate a characteristic clustering feature of invasive tumor growth, a property we attribute to "self-metastatic" growth. When the additional influence of directed migrations under chemotactic environments are considered, we find that tumor growth and invasive morphology are supported while the tumor is distant from the source, but are progressively discouraged as the tumor converges about that source.Conclusions: We show that invasive clustering can derive from basic kinetic assumptions often neglected in more complex models. While higher-order mechanisms, e. g. directed migration upon chemotactic stimuli, may result in clustering growth morphologies, exclusive attributions of this phenotype to this or other structured microenvironments would be inappropriate, in light of our finding these features are observable in a homogeneous environment. Furthermore, directed migration will result in loss of the invasive phenotype as the tumor approaches the attractor source. Reviewers: This article was reviewed by Mark Little and Glen Webb.