Computational investigation of intrinsic and extrinsic mechanisms underlying the formation of carcinoma
Computational investigation of intrinsic and extrinsic mechanisms underlying the formation of carcinoma
复制标题
DOI：
10.1093/imammb/dqq021
复制
发表时间：
2012-03-01
影响因子：
1.1
通讯作者：
Anderson, Alexander R. A.
中科院分区：
文献类型：
--
作者：
Rejniak, Katarzyna A.;Quaranta, Vito;Anderson, Alexander R. A.
组织上皮结构的破坏被认为与癌症的发生有关;然而，对早期肿瘤性病变的细胞生物学知之甚少。计算模型可以通过模拟肿瘤发生的不同情况和通过计算机测试各种内在和外在因素对新兴多细胞形态的影响来促进早期癌症阶段的研究。在这里，我们已经使用了一个计算模型来创建3D形态图，多细胞形态的集合所产生的系统修改的三个模型参数定义细胞敏感性的细胞生长，死亡和粘附到细胞外基质的外部线索。该系统性检索揭示了形成稳健上皮结构的参数值范围以及导致类似肿瘤样形态的异常几何形状的参数值范围。我们还展示了我们的模型如何通过细胞敏感性参数空间将实验性多细胞系统的形态映射到其计算机上的对应物上，这反过来又使我们能够识别导致这些形态扭曲的遗传或表观遗传变化。
The disruption of tissue epithelial architecture is thought to be involved in the initiation of cancer; however, little is known about the cell biology of early neoplastic lesions. Computational models can facilitate in the study of early cancer stagesby simulating different scenarios of tumour inception and by testing in silico the influence of various intrinsic and extrinsic factors on the emerging multicellular morphologies. Here, we have used a computational model to create 3D morphocharts, collections of multicellular morphologies arising from systematic modification of three model parameters defining cell sensitivity to external cues for cell growth, death and adhesion to the extracellular matrix. This systematic search revealed the ranges of parameter values for which robust epithelial structures formed and those that led to abnormal geometrical forms resembling tumour-like morphologies. We also showed how our model can be used to map morphologies of experimental multicellular systems onto their in silico counterpart via the cell sensitivity parameter space that may in turn allow us to identify genetic or epigenetic changes responsible for these morphological distortions.