Michor Franziska, Nowak Martin A, Iwasa Yoh
Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, MA 02138, USA.
J Theor Biol. 2006 Jun 21;240(4):521-30. doi: 10.1016/j.jtbi.2005.10.021. Epub 2005 Dec 15.
Tumor metastasis accounts for the majority of deaths in cancer patients. The metastatic behavior of cancer cells is promoted by mutations in many genes, including activation of oncogenes such as RAS and MYC. Here, we develop a mathematical framework to analyse the dynamics of mutations enabling cells to metastasize. We consider situations in which one mutation is necessary to confer metastatic ability to the cell. We study different population sizes of the main tumor and different somatic fitness values of metastatic cells. We compare mutations that are positively selected in the main tumor with those that are neutral or negatively selected, but faster at forming metastases. We study whether metastatic potential is the property of all (or the majority of) cells in the main tumor or only the property of a small subset. Our theory shows how to calculate the expected number of metastases that are formed by a tumor.
肿瘤转移是癌症患者死亡的主要原因。癌细胞的转移行为由许多基因的突变所促进，包括RAS和MYC等癌基因的激活。在此，我们开发了一个数学框架来分析使细胞能够转移的突变动态。我们考虑了赋予细胞转移能力需要一个突变的情况。我们研究了主肿瘤的不同群体大小以及转移细胞的不同体细胞适应度值。我们将在主肿瘤中被正向选择的突变与那些中性或负向选择但形成转移更快的突变进行比较。我们研究转移潜能是主肿瘤中所有（或大多数）细胞的属性还是仅一小部分细胞的属性。我们的理论展示了如何计算肿瘤形成转移灶的预期数量。
