Evolution of uncontrolled proliferation and the angiogenic switch in cancer
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'...
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AIMS Press
2012-09-01
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| Series: | Mathematical Biosciences and Engineering |
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| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2012.9.843 |
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| author | John D. Nagy Dieter Armbruster |
| author_facet | John D. Nagy Dieter Armbruster |
| author_sort | John D. Nagy |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-18392933cdaf4db884b8e3947aad47bf |
| institution | Kabale University |
| issn | 1551-0018 |
| language | English |
| publishDate | 2012-09-01 |
| publisher | AIMS Press |
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| series | Mathematical Biosciences and Engineering |
| spelling | doaj-art-18392933cdaf4db884b8e3947aad47bf2025-01-24T02:07:06ZengAIMS PressMathematical Biosciences and Engineering1551-00182012-09-019484387610.3934/mbe.2012.9.843Evolution of uncontrolled proliferation and the angiogenic switch in cancerJohn D. Nagy0Dieter Armbruster1Department of Life Sciences, Scottsdale Community College, 9000 E. Chaparral Rd., Scottsdale, AZ 85256Department of Life Sciences, Scottsdale Community College, 9000 E. Chaparral Rd., Scottsdale, AZ 85256The 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.https://www.aimspress.com/article/doi/10.3934/mbe.2012.9.843evolutionary suicideadaptive dynamicsenergy chargemultiscale modelsperturbation expansion.canceratp |
| spellingShingle | John D. Nagy Dieter Armbruster Evolution of uncontrolled proliferation and the angiogenic switch in cancer Mathematical Biosciences and Engineering evolutionary suicide adaptive dynamics energy charge multiscale models perturbation expansion. cancer atp |
| title | Evolution of uncontrolled proliferation and the angiogenic switch in cancer |
| title_full | Evolution of uncontrolled proliferation and the angiogenic switch in cancer |
| title_fullStr | Evolution of uncontrolled proliferation and the angiogenic switch in cancer |
| title_full_unstemmed | Evolution of uncontrolled proliferation and the angiogenic switch in cancer |
| title_short | Evolution of uncontrolled proliferation and the angiogenic switch in cancer |
| title_sort | evolution of uncontrolled proliferation and the angiogenic switch in cancer |
| topic | evolutionary suicide adaptive dynamics energy charge multiscale models perturbation expansion. cancer atp |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2012.9.843 |
| work_keys_str_mv | AT johndnagy evolutionofuncontrolledproliferationandtheangiogenicswitchincancer AT dieterarmbruster evolutionofuncontrolledproliferationandtheangiogenicswitchincancer |