The role of transforming growth factor-beta-mediated tumor-stroma interactions in prostate cancer progression: an integrative approach.
The role of transforming growth factor-beta-mediated tumor-stroma interactions in prostate cancer progression: an integrative approach.
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DOI：
10.1158/0008-5472.can-08-3957
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发表时间：
2009-09-01
期刊：
影响因子：
11.2
通讯作者：
Anderson AR
中科院分区：
文献类型：
--
作者：
Basanta D;Strand DW;Lukner RB;Franco OE;Cliffel DE;Ayala GE;Hayward SW;Anderson AR
我们已经实现了一个混合细胞自动机（HCA）模型的基础上，人类前列腺的结构，概括了关键的相互作用，在新生肿瘤病灶之间的肿瘤细胞和相邻的基质。模型模拟演示了肿瘤细胞和基质之间的随机相互作用如何导致肿瘤生长的结构抑制、适度增殖或无对抗的肿瘤生长。该模型结合了前列腺肿瘤进展的关键方面，包括TGF-β和基质降解酶（MDE）活性以及基质活化。它还检查了TGF-β在肿瘤进展过程中的重要性以及基质细胞密度在调节肿瘤生长中的作用。在体内测试了模型关于上皮TGF-β产生对腺体稳定性的影响的关键预测之一的有效性。这些实验结果证实了该模型除了提供实验兴趣的新途径之外，还能够生成可测试的生物预测。这项工作强调了对更具病理代表性的模型的需求，以合作驱动计算和生物建模，最终可能导致更准确的前列腺癌诊断和治疗。
We have implemented a hybrid cellular automata (HCA) model based upon the structure of human prostate that recapitulates key interactions in nascent tumor foci between tumor cells and adjacent stroma. Model simulations demonstrate how stochastic interactions between tumor cells and stroma may lead to; a structural suppression of tumor growth, modest proliferation, or, unopposed tumor growth. The model incorporates key aspects of prostate tumor progression including TGF-β and matrix degrading enzyme (MDE) activity, and stromal activation. It also examines the importance of TGF-β during tumor progression and the role of stromal cell density in regulating tumour growth. The validity of one of the model’s key predictions concerning the effect of epithelial TGF-β production on glandular stability was tested in vivo. These experimental results confirmed the ability of the model to generate testable biological predictions in addition to providing new avenues of experimental interest. This work underscores the need for more pathologically representative models to cooperatively drive computational and biological modelling, which together could eventually lead to more accurate diagnoses and treatments of prostate cancer.