Peng Hsin-Hsin, Dong Cheng
Department of Bioengineering, Pennsylvania State University, 233 Hallowell Bldg., University Park, PA 16802, USA.
Cell Mol Bioeng. 2009 Sep 1;2(3):375-385. doi: 10.1007/s12195-009-0067-5.
It has been shown in our previous study that melanoma cells induce junction disassembly in the manner related to phospholipase C-calcium activation. In light of this observation, we have developed a mathematical model of the signaling pathway and adapted multi-parametric sensitivity analysis (MPSA) to identify important parameters in the model, which examines tumor cell-induced calcium mobilization in endothelial cells. The objective functions, with respect to individual parameters, were generated for the calcium mobilization model and MPSA was performed according to the function. The results showed that sarco/endoplasmic reticulum calcium ATPase was one of the putative key factors in regulating calcium mobilization. The model is a proof of concept of systemic analysis of a signaling network, and the results may have practical applications in describing how endothelial cells respond to tumor cells. Taken together, we have devised numerical means to macroscopically study roles of calcium signaling in endothelial cells in contact with metastatic tumor cells.
我们之前的研究表明，黑色素瘤细胞以与磷脂酶C - 钙激活相关的方式诱导连接解离。鉴于这一观察结果，我们开发了一种信号通路的数学模型，并采用多参数敏感性分析（MPSA）来识别模型中的重要参数，该模型研究肿瘤细胞诱导的内皮细胞钙动员。针对钙动员模型生成了关于各个参数的目标函数，并根据该函数进行了MPSA。结果表明，肌浆网/内质网钙ATP酶是调节钙动员的推定关键因素之一。该模型是信号网络系统分析概念验证，其结果可能在描述内皮细胞如何响应肿瘤细胞方面具有实际应用。综上所述，我们设计了数值方法来宏观研究钙信号在与转移性肿瘤细胞接触的内皮细胞中的作用。
