Vanderbilt Prostate Cancer Center, Department of Urologic Surgery, Vanderbilt University Medical Center, AA-1309 Medical Center North, Nashville, TN 37232, USA.
Curr Mol Med. 2010 Feb;10(1):95-112. doi: 10.2174/156652410791065363.
From the morphogenetic movements of the three germ layers during development to the reactive stromal microenvironment in cancer, tissue interactions are vital to maintaining healthy organ morphologic architecture and function. The stromal compartment is thought to be complicit in tumor progression and, as such, represents an opportune target for disease therapies. However, recent developments in our understanding of the diversity of the stromal compartment and the lack of appropriate models to study its relevance in human disease have limited our further understanding of the role of tissue interactions in tumor progression. The failure any model to fully recapitulate the complexities of systemic biology continue to create a higher imperative for incorporating various perspectives into a broader understanding for the ultimate goal of designing interventional therapies. Understanding this potential, this review examines the biological models used to study stromal-epithelial interactions and includes an attempt to incorporate behavioral terminology to define and mathematically model ecological relationships in stromal-epithelial interactions. In addition, the current attempt to incorporate these diverse ecological perspectives into in silico mathematical models through cross-disciplinary coordination is reviewed, which will provide a fresh perspective on defining cell group behavior and tissue ecology in disease and hopefully lead to the generation of new hypotheses to be empirically validated.
从发育过程中三个胚层的形态发生运动到癌症中的反应性基质微环境,组织相互作用对于维持健康器官形态结构和功能至关重要。基质区室被认为是肿瘤进展的同谋,因此,它是疾病治疗的一个有吸引力的靶点。然而,我们对基质区室多样性的理解的最新进展,以及缺乏适当的模型来研究其在人类疾病中的相关性,限制了我们对组织相互作用在肿瘤进展中的作用的进一步理解。任何模型都无法完全再现系统生物学的复杂性,这继续要求我们将各种观点纳入更广泛的理解,以最终实现设计干预治疗的目标。了解到这一潜力,本文考察了用于研究基质-上皮相互作用的生物学模型,并尝试采用行为学术语来定义和数学建模基质-上皮相互作用中的生态关系。此外,本文还回顾了目前通过跨学科协调将这些不同的生态观点纳入计算数学模型的尝试,这将为定义疾病中细胞群体行为和组织生态学提供新的视角,并有望产生新的假说,以供经验验证。