BioMaPS Institute, Rutgers University, Piscataway, NJ 08854, USA.
J Theor Biol. 2010 Apr 21;263(4):393-406. doi: 10.1016/j.jtbi.2009.11.024. Epub 2009 Dec 16.
Ductal carcinoma in situ (DCIS) of the breast is a non-invasive tumor in which cells proliferate abnormally, but remain confined within a duct. Although four distinguishable DCIS morphologies are recognized, the mechanisms that generate these different morphological classes remain unclear, and consequently the prognostic strength of DCIS classification is not strong. To improve the understanding of the relation between morphology and time course, we have developed a 2D in silico particle model of the growth of DCIS within a single breast duct. This model considers mechanical effects such as cellular adhesion and intra-ductal pressure, and biological features including proliferation, apoptosis, necrosis, and cell polarity. Using this model, we find that different regions of parameter space generate distinct morphological subtypes of DCIS, so elucidating the relation between morphology and time course. Furthermore, we find that tumors with similar architectures may in fact be produced through different mechanisms, and we propose future work to further disentangle the mechanisms involved in DCIS progression.
乳腺导管原位癌 (DCIS) 是一种非浸润性肿瘤，其中细胞异常增殖，但仍局限于导管内。尽管已经识别出四种可区分的 DCIS 形态，但产生这些不同形态类别的机制仍不清楚，因此 DCIS 分类的预后强度并不强。为了更好地理解形态与时间进程之间的关系，我们开发了一种 2D 计算机模拟粒子模型，用于模拟乳腺导管内 DCIS 的生长。该模型考虑了细胞黏附和管内压力等力学效应，以及增殖、凋亡、坏死和细胞极性等生物学特征。使用该模型，我们发现不同的参数空间区域会产生不同的 DCIS 形态亚型，从而阐明形态与时间进程之间的关系。此外，我们发现具有相似结构的肿瘤实际上可能是通过不同的机制产生的，我们提出了进一步的工作来进一步厘清 DCIS 进展中涉及的机制。
