School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
Philos Trans A Math Phys Eng Sci. 2020 May 15;378(2171):20190244. doi: 10.1098/rsta.2019.0244. Epub 2020 Apr 13.
Although cancerous tumours usually originate from a single cell, they normally evolve into a remarkably heterogeneous agglomeration of cells. Heterogeneity is a pervasive and almost universal feature of tumours, but its origin and consequences remain poorly understood. Tumour heterogeneity has been usually associated with poor prognosis, but a better understanding of it may lead to more personalized diagnosis and therapy. Here, we study tumour heterogeneity developing a computational model in which different cell subpopulations compete for space. The model suggests that aggressive tumour subpopulations may become even more aggressive when they grow with a non-aggressive subpopulation. The model also provides a mechanistic explanation of how heterogeneity drives growth. In particular, we observed that even a mild heterogeneity in the proliferation rates of different cell subpopulations leads to a much faster overall tumour growth when compared to a homogeneous tumour. The proposed model may be a starting point to study tumour heterogeneity computationally and to suggest new hypotheses to be tested experimentally. This article is part of the theme issue 'Patterns in soft and biological matters'.
虽然癌性肿瘤通常起源于单个细胞，但它们通常会演变成一个显著异质的细胞聚集物。异质性是肿瘤的普遍特征，但它的起源和后果仍知之甚少。肿瘤异质性通常与预后不良有关，但对其更好的理解可能会导致更个性化的诊断和治疗。在这里，我们通过建立一个计算模型来研究肿瘤异质性，在该模型中，不同的细胞亚群为争夺空间而竞争。该模型表明，当具有侵袭性的肿瘤亚群与非侵袭性的亚群一起生长时，它们可能会变得更具侵袭性。该模型还提供了一个关于异质性如何驱动生长的机制解释。具体来说，我们观察到，即使不同细胞亚群的增殖率存在轻微的异质性，与同质肿瘤相比，也会导致肿瘤的整体生长速度大大加快。所提出的模型可能是一个起点，用于在计算上研究肿瘤异质性，并提出新的假设进行实验验证。本文是“软物质和生物物质中的模式”专题的一部分。
