Microenvironmental Independence Associated with Tumor Progression
Microenvironmental Independence Associated with Tumor Progression
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DOI：
10.1158/0008-5472.can-09-0437
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发表时间：
2009-11-15
期刊：
影响因子：
11.2
通讯作者：
Weaver, Alissa M.
中科院分区：
文献类型：
--
作者：
Anderson, Alexander R. A.;Hassanein, Mohamed;Weaver, Alissa M.
肿瘤-微环境相互作用越来越多地被认为会影响肿瘤的进展。为了了解肿瘤细胞在不同微环境中的竞争动力学，我们实验性地参数化了一个混合离散-连续数学模型，该模型具有来自一组具有正常、转化或致瘤特性的相关乳腺细胞系的表型性状数据。令人惊讶的是，在资源丰富的微环境中，对增殖或迁移几乎没有限制，转化的（但不是致瘤的）细胞是最成功的，并且在异质性肿瘤模拟中胜过其他细胞类型。相反，空间和/或生长因子限制的受限微环境对来自致瘤细胞系的表型提供了选择性优势。分析每种表型在受限微环境与不受限微环境中的相对性能发现，尽管所有细胞类型在资源受限微环境中生长较慢，但最具侵略性的细胞受微环境限制的影响最小。测试微环境资源可用性和竞争性细胞动力学之间的关系的博弈论模型支持的概念，即微环境的独立性是一个有利的细胞特性，在资源有限的微环境。[Cancer Res 2009;69（22）：8797-806]
Tumor-microenvironment interactions are increasingly recognized to influence tumor progression. To understand the competitive dynamics of tumor cells in diverse microenvironments, we experimentally parameterized a hybrid discrete-continuum mathematical model with phenotypic trait data from a set of related mammary cell lines with normal, transformed, or tumorigenic properties. Surprisingly, in a resource-rich microenvironment, with few limitations on proliferation or migration, transformed (but not tumorigenic) cells were most successful and outcompeted other cell types in heterogeneous tumor simulations. Conversely, constrained microenvironments with limitations on space and/or growth factors gave a selective advantage to phenotypes derived from tumorigenic cell lines. Analysis of the relative performance of each phenotype in constrained versus unconstrained microenvironments revealed that, although all cell types grew more slowly in resource-constrained microenvironments, the most aggressive cells were least affected by microenvironmental constraints. A game theory model testing the relationship between microenvironment resource availability and competitive cellular dynamics supports the concept that microenvironmental independence is an advantageous cellular trait in resource-limited microenvironments. [Cancer Res 2009;69(22):8797-806]