Brú Antonio, Albertos Sonia, Luis Subiza José, García-Asenjo José López, Brú Isabel
CCMA, Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain.
Biophys J. 2003 Nov;85(5):2948-61. doi: 10.1016/S0006-3495(03)74715-8.
Scaling techniques were used to analyze the fractal nature of colonies of 15 cell lines growing in vitro as well as of 16 types of tumor developing in vivo. All cell colonies were found to exhibit exactly the same growth dynamics-which correspond to the molecular beam epitaxy (MBE) universality class. MBE dynamics are characterized by 1), a linear growth rate, 2), the constraint of cell proliferation to the colony/tumor border, and 3), surface diffusion of cells at the growing edge. These characteristics were experimentally verified in the studied colonies. That these should show MBE dynamics is in strong contrast with the currently established concept of tumor growth: the kinetics of this type of proliferation rules out exponential or Gompertzian growth. Rather, a clear linear growth regime is followed. The importance of new cell movements-cell diffusion at the tumor border-lies in the fact that tumor growth must be conceived as a competition for space between the tumor and the host, and not for nutrients or other factors. Strong experimental evidence is presented for 16 types of tumor, the growth of which cell surface diffusion may be the main mechanism responsible in vivo. These results explain most of the clinical and biological features of colonies and tumors, offer new theoretical frameworks, and challenge the wisdom of some current clinical strategies.
采用标度技术分析了15种体外生长的细胞系集落以及16种体内生长的肿瘤的分形性质。发现所有细胞集落均呈现完全相同的生长动力学——这与分子束外延(MBE)普适类相对应。MBE动力学的特征为:1)线性生长速率;2)细胞增殖局限于集落/肿瘤边界;3)生长边缘处细胞的表面扩散。这些特征在研究的集落中得到了实验验证。这些集落呈现MBE动力学与当前已确立的肿瘤生长概念形成了强烈对比:这种增殖动力学排除了指数生长或Gompertzian生长。相反,呈现出明显的线性生长模式。新的细胞运动——肿瘤边界处的细胞扩散——的重要性在于,肿瘤生长必须被视为肿瘤与宿主之间对空间的竞争,而非对营养物质或其他因素的竞争。针对16种肿瘤给出了有力的实验证据,其体内生长的主要机制可能是细胞表面扩散。这些结果解释了集落和肿瘤的大多数临床和生物学特征,提供了新的理论框架,并对当前一些临床策略的合理性提出了挑战。