Zhu Xiaomei, Yuan Ruoshi, Hood Leroy, Ao Ping
GeneMath, 5525 27th Ave. N.E., Seattle, WA 98105, USA.
Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Prog Biophys Mol Biol. 2015 Jan;117(1):30-42. doi: 10.1016/j.pbiomolbio.2015.01.004. Epub 2015 Feb 3.
We explored endogenous molecular-cellular network hypothesis for prostate cancer by constructing relevant endogenous interaction network model and analyzing its dynamical properties. Molecular regulations involved in cell proliferation, apoptosis, differentiation and metabolism are included in a hierarchical mathematical modeling scheme. This dynamical network organizes into multiple robust functional states, including physiological and pathological ones. Some states have characteristics of cancer: elevated metabolic and immune activities, high concentration of growth factors and different proliferative, apoptotic and adhesive behaviors. The molecular profile of calculated cancer state agrees with existing experiments. The modeling results have additional predictions which may be validated by further experiment: 1) Prostate supports both stem cell like and liver style proliferation; 2) While prostate supports multiple cell types, including basal, luminal and endocrine cell type differentiated from its stem cell, luminal cell is most likely to be transformed malignantly into androgen independent type cancer; 3) Retinoic acid pathway and C/EBPα are possible therapeutic targets.
我们通过构建相关的内源性相互作用网络模型并分析其动力学特性，探索了前列腺癌的内源性分子-细胞网络假说。细胞增殖、凋亡、分化和代谢中涉及的分子调控被纳入一个分层数学建模方案。这个动态网络组织成多种稳健的功能状态，包括生理和病理状态。一些状态具有癌症的特征：代谢和免疫活动增强、生长因子浓度高以及不同的增殖、凋亡和黏附行为。计算得出的癌症状态的分子特征与现有实验结果相符。建模结果还有其他可通过进一步实验验证的预测：1）前列腺既支持干细胞样增殖，也支持肝样增殖；2）虽然前列腺支持多种细胞类型，包括从其干细胞分化而来的基底细胞、管腔细胞和内分泌细胞类型，但管腔细胞最有可能恶性转化为雄激素非依赖型癌症；3）视黄酸途径和C/EBPα可能是治疗靶点。
