Evolution of uncontrolled proliferation and the angiogenic switch in cancer

  • Received: 01 February 2012 Accepted: 29 June 2018 Published: 01 October 2012
  • MSC : Primary: 92C40, 92D15.

  • The major goal of evolutionary oncology is to explain how malignant traits evolve to become cancer "hallmarks." One such hallmark---the angiogenic switch---is difficult to explain for the same reason altruism is difficult to explain. An angiogenic clone is vulnerable to "cheater" lineages that shunt energy from angiogenesis to proliferation, allowing the cheater to outcompete cooperative phenotypes in the environment built by the cooperators. Here we show that cell- or clone-level selection is sufficient to explain the angiogenic switch, but not because of direct selection on angiogenesis factor secretion---angiogenic potential evolves only as a pleiotropic afterthought. We study a multiscale mathematical model that includes an energy management system in an evolving angiogenic tumor. The energy management model makes the counterintuitive prediction that ATP concentration in resting cells increases with increasing ATP hydrolysis, as seen in other theoretical and empirical studies. As a result, increasing ATP hydrolysis for angiogenesis can increase proliferative potential, which is the trait directly under selection. Intriguingly, this energy dynamic allows an evolutionary stable angiogenesis strategy, but this strategy is an evolutionary repeller, leading to runaway selection for extreme vascular hypo- or hyperplasia. The former case yields a tumor-on-a-tumor, or hypertumor, as predicted in other studies, and the latter case may explain vascular hyperplasia evident in certain tumor types.

    Citation: John D. Nagy, Dieter Armbruster. Evolution of uncontrolled proliferation and the angiogenic switch in cancer[J]. Mathematical Biosciences and Engineering, 2012, 9(4): 843-876. doi: 10.3934/mbe.2012.9.843

    Related Papers:

  • The major goal of evolutionary oncology is to explain how malignant traits evolve to become cancer "hallmarks." One such hallmark---the angiogenic switch---is difficult to explain for the same reason altruism is difficult to explain. An angiogenic clone is vulnerable to "cheater" lineages that shunt energy from angiogenesis to proliferation, allowing the cheater to outcompete cooperative phenotypes in the environment built by the cooperators. Here we show that cell- or clone-level selection is sufficient to explain the angiogenic switch, but not because of direct selection on angiogenesis factor secretion---angiogenic potential evolves only as a pleiotropic afterthought. We study a multiscale mathematical model that includes an energy management system in an evolving angiogenic tumor. The energy management model makes the counterintuitive prediction that ATP concentration in resting cells increases with increasing ATP hydrolysis, as seen in other theoretical and empirical studies. As a result, increasing ATP hydrolysis for angiogenesis can increase proliferative potential, which is the trait directly under selection. Intriguingly, this energy dynamic allows an evolutionary stable angiogenesis strategy, but this strategy is an evolutionary repeller, leading to runaway selection for extreme vascular hypo- or hyperplasia. The former case yields a tumor-on-a-tumor, or hypertumor, as predicted in other studies, and the latter case may explain vascular hyperplasia evident in certain tumor types.


    加载中
  • Reader Comments
  • © 2012 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(2468) PDF downloads(559) Cited by(13)

Article outline

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog