Bridging population and tissue scale tumor dynamics: a new paradigm for understanding differences in tumor growth and metastatic disease.
Bridging population and tissue scale tumor dynamics: a new paradigm for understanding differences in tumor growth and metastatic disease.
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DOI：
10.1158/0008-5472.can-13-0759
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发表时间：
2014-01-15
期刊：
影响因子：
11.2
通讯作者：
Anderson ARA
中科院分区：
文献类型：
--
作者：
Gallaher J;Babu A;Plevritis S;Anderson ARA
为了更好地理解原发肿瘤生长速度和转移负担之间的关系，我们提出了一种方法，将从SEER数据库中提取的人群水平的肿瘤生长动力学与组织水平的肿瘤生长动力学联系起来。具体地说，通过这种方法，我们能够将从人群水平模型得出的肿瘤生长率和转移负荷的估计与从组织水平模型得出的原发肿瘤血管反应和循环肿瘤细胞(CTC)分数的估计联系起来。人群水平模型参数的变化会导致癌症特异性存活率和治愈率的差异。组织水平模型参数的变化产生不同的原发肿瘤动力学，从而导致CTCs不同的生长动力学。将我们的方法分别应用于肺癌和乳腺癌，并对结果进行了比较。人口模型表明，肺癌生长较快，在较小的体积下会脱落大量致命的转移细胞，而乳腺癌生长较慢，在变大之前不会显著脱落致命的转移细胞。尽管组织水平模型没有明确地模拟转移人口，但我们能够通过引入CTC人口作为中介并假设相关性，从而摆脱转移负担对原发肿瘤生长的直接依赖。我们校准了组织水平模型，以产生与群体模型一致的结果，同时也揭示了原发肿瘤和CTC之间更动态的关系。这导致肺部肿瘤呈指数增长，乳腺肿瘤呈指数增长。我们的结论是，原发肿瘤的血管反应在原发肿瘤和CTCs的动力学中都是主要的参与者，并且在乳腺癌和肺癌中有显著的不同。
To provide a better understanding of the relationship between primary tumor growth rates and metastatic burden, we present a method that bridges tumor growth dynamics at the population-level, extracted from the SEER database, to those at the tissue level. Specifically, with this method, we are able to relate estimates of tumor growth rates and metastatic burden derived from a population level model to estimates of the primary tumor vascular response and the circulating tumor cell (CTC) fraction derived from a tissue level model. Variation in the population level model parameters produce differences in cancer-specific survival and cure fraction. Variation in the tissue level model parameters produces different primary tumor dynamics that subsequently lead to different growth dynamics of the CTCs. Our method to bridge the population and tissue scales was applied to lung and breast cancer separately, and the results were compared. The population model suggests that lung tumors grow faster and shed a significant number of lethal metastatic cells at small sizes, whereas breast tumors grow slower and do not significantly shed lethal metastatic cells until becoming larger. Although the tissue level model does not explicitly model the metastatic population, we are able to disengage the direct dependency of the metastatic burden on primary tumor growth by introducing the CTC population as an intermediary and assuming dependency. We calibrate the tissue level model to produce results consistent with the population model while also revealing a more dynamic relationship between the primary tumor and the CTCs. This leads to exponential tumor growth in lung and power law tumor growth in breast. We conclude that the vascular response of the primary tumor is a major player in the dynamics of both the primary tumor and the CTCs, and is significantly different in breast and lung cancer.