Pattern of self-organization in tumour systems: complex growth dynamics in a novel brain tumour spheroid model
Pattern of self-organization in tumour systems: complex growth dynamics in a novel brain tumour spheroid model
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DOI：
10.1046/j.1365-2184.2001.00202.x
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发表时间：
2001-04-01
影响因子：
8.5
通讯作者：
Chiocca, EA
中科院分区：
文献类型：
--
作者：
Deisboeck, TS;Berens, ME;Chiocca, EA
我们认为，高度恶性的脑瘤是一个机会性、自组织和适应性的复杂动态生物系统，而不是一个无组织的细胞团。为了验证细胞增殖和侵袭等相关关键行为的假说，我们开发了一种新的体外测试，能够在相同的实验设置下显示这个多参数系统的几个动态特征。本实验研究了多细胞U87MGmESFR球体在特定的细胞外基质凝胶中随时间的发展。结果表明，体积生长和细胞侵袭等关键特征可以在相同的环境下分析超过144h，而不需要持续补充额外的营养。此外，肿瘤的增殖和侵袭是密切相关的，这两个关键特征随着时间的推移建立了不同的比率，以实现最大的细胞速度并保持系统的时空扩展动力学。单细胞侵袭遵循链状模式，导致了分支内同型吸引的新概念。由于初步研究表明，异型吸引可以特异性地指导和加速新出现的侵袭网络：我们进一步引入了最小阻力、最大允许和最高吸引的概念，作为肿瘤侵袭的基本原则。总而言之，这些结果支持了自组织自适应生物系统的假设。
We propose that a highly malignant brain tumour is an opportunistic, self-organizing and adaptive complex dynamic biosystem rather than an unorganized cell mass. To test the hypothesis of related key behaviour such as cell proliferation and invasion, we have developed a new in vitro assay capable of displaying several of the dynamic features of this multiparameter system in the same experimental setting. This assay investigates the development of multicellular U87MGmESFR spheroids in a specific extracellular matrix gel over time. The results show that key features such as volumetric growth and cell invasion can be analysed in the same setting over 144 h without continuously supplementing additional nutrition. Moreover, tumour proliferation and invasion are closely correlated and both key features establish a distinct ratio over time to achieve maximum cell velocity and to maintain the system's temporo-spatial expansion dynamics. Single cell invasion follows a chain-like pattern leading to the new concept of a intrabranch homotype attraction. Since preliminary studies demonstrate that heterotype attraction can specifically direct and accelerate the emerging invasive network: we further introduce the concept of least resistance, most permission and highest attraction as an essential principle for tumour invasion. Together, these results support the hypothesis of a self-organizing adaptive biosystem.