Plausibility of stromal initiation of epithelial cancers without a mutation in the epithelium: a computer simulation of morphostats
Plausibility of stromal initiation of epithelial cancers without a mutation in the epithelium: a computer simulation of morphostats
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DOI：
10.1186/1471-2407-9-89
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发表时间：
2009-03-23
期刊：
影响因子：
3.8
通讯作者：
Kramer, Barnett S.
中科院分区：
文献类型：
--
作者：
Baker, Stuart G.;Soto, Ana M.;Kramer, Barnett S.
背景资料：动物模型的实验证据支持这样的观点，即基质和上皮之间相互作用的破坏在癌发生的起始中起重要作用。这些被破坏的相互作用被假设为介导的分子，称为morphostats，通过组织扩散，以确定细胞表型和维持组织architecture.Methods：我们开发了一个基于细胞更新和morphostats的简单属性的计算机模拟。在计算机模拟下，间质中morphostat梯度的破坏产生癌的上皮前体，而上皮中没有任何突变。该模型与肿瘤中发现的遗传和表观遗传变化的积累可能在异常细胞的创始人群体形成后出现的可能性一致，异常细胞定义为由低或不足的morphostat水平产生并且不再对morphostat浓度产生反应的细胞。由于该模型在生物学上是合理的，我们希望这些结果将刺激进一步的实验。
Background: There is experimental evidence from animal models favoring the notion that the disruption of interactions between stroma and epithelium plays an important role in the initiation of carcinogenesis. These disrupted interactions are hypothesized to be mediated by molecules, termed morphostats, which diffuse through the tissue to determine cell phenotype and maintain tissue architecture.Methods: We developed a computer simulation based on simple properties of cell renewal and morphostats.Results: Under the computer simulation, the disruption of the morphostat gradient in the stroma generated epithelial precursors of cancer without any mutation in the epithelium.Conclusion: The model is consistent with the possibility that the accumulation of genetic and epigenetic changes found in tumors could arise after the formation of a founder population of aberrant cells, defined as cells that are created by low or insufficient morphostat levels and that no longer respond to morphostat concentrations. Because the model is biologically plausible, we hope that these results will stimulate further experiments.