Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology (IPMB) and Bioquant, Heidelberg University, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
Sci Rep. 2011;1:31. doi: 10.1038/srep00031. Epub 2011 Jul 6.
With countless biological details emerging from cancer experiments, there is a growing need for minimal mathematical models which simultaneously advance our understanding of single tumors and metastasis, provide patient-personalized predictions, whilst avoiding excessive hard-to-measure input parameters which complicate simulation, analysis and interpretation. Here we present a model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in a murine mammary cell line EMT6-HER2 model in BALB/c mice and with clinical metastasis data. Seeding data about the tumor and its vasculature from in vivo images, our model predicts corridors of future tumor growth behavior and intervention response. A scaling relation enables the estimation of a tumor's most likely evolution and pinpoints specific target sites to control growth. Our findings suggest that the clinically separate phenomena of individual tumor growth and metastasis can be viewed as mathematical copies of each other differentiated only by network structure.
随着癌症实验中无数生物学细节的出现,我们越来越需要最小化的数学模型,这些模型既要能够同时推进我们对单个肿瘤和转移的理解,提供针对患者个体的预测,又要避免因过度使用难以测量的输入参数而使模拟、分析和解释变得复杂。在这里,我们提出了一个围绕着共同进化的资源网络和细胞群体的模型,该模型与 BALB/c 小鼠中的 EMT6-HER2 鼠乳腺细胞系原发性肿瘤以及临床转移数据吻合良好。通过对来自体内图像的肿瘤及其脉管系统的播种数据,我们的模型预测了未来肿瘤生长行为和干预反应的通道。一个比例关系可以用来估计肿瘤最有可能的进化,并确定特定的靶标来控制生长。我们的研究结果表明,临床上单独的肿瘤生长和转移现象可以被看作是彼此的数学副本,只是网络结构不同。