Evolution of cooperation among tumor cells
Evolution of cooperation among tumor cells
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DOI：
10.1073/pnas.0606053103
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发表时间：
2006-09-05
影响因子：
11.1
通讯作者：
Pienta, Kenneth J.
中科院分区：
文献类型：
--
作者：
Axelrod, Robert;Axelrod, David E.;Pienta, Kenneth J.
合作的演化有一个完善的基于博弈论的理论框架。这一方法为政治学、经济学和进化生物学等多种学科做出了宝贵的贡献。现有的癌症理论表明，癌细胞的个体克隆相互独立地进化，获得形成恶性肿瘤所需的所有遗传特征或标志。现在还认识到肿瘤是异型的，癌细胞与组织微环境中的正常基质细胞相互作用，包括内皮细胞、基质细胞和神经细胞。这种肿瘤细胞与基质细胞的相互作用本身就是一种恶性肿瘤，因为已经证明这些非恶性细胞支持甚至使肿瘤生长成为可能。在这里，我们通过将肿瘤细胞视为游戏玩家来补充这一理论，这些游戏玩家的相互作用有助于确定它们的达尔文适应性。我们收集了肿瘤细胞通过扩散产物克服某些宿主防御的证据。我们最初的贡献是提出了两个相邻的细胞可以相互保护免受一系列宿主防御的可能性，而这两个细胞都不能单独生存。合作可以演变为遗传多样性肿瘤细胞之间的副产品互利共生。我们的假设补充了，但并没有取代，传统的观点认为，一个克隆群体的细胞发展的所有必要的遗传性状独立形成肿瘤。通过共享扩散产物的合作提出了关于肿瘤发生的新问题，并对理解观察到的现象，设计新的实验和开发新的治疗方法产生了影响。
The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.