Stromal reactivity differentially drives tumour cell evolution and prostate cancer progression
Prostate cancer (PCa) progression is a complex eco-evolutionary process driven by the feedback between evolving tumour cell phenotypes and microenvironmentally driven selection. To better understand this relationship, we used a multiscale mathematical model that integrates data from biology and pathology on the microenvironmental regulation of PCa cell behaviour. Our data indicate that the interactions between tumour cells and their environment shape the evolutionary dynamics of PCa cells and explain overall tumour aggressiveness. A key environmental determinant of this aggressiveness is the stromal ecology, which can be either inhibitory, highly reactive (supportive) or non-reactive (neutral). Our results show that stromal ecology correlates directly with tumour growth but inversely modulates tumour evolution. This suggests that aggressive, environmentally independent PCa may be a result of poor stromal ecology, supporting the concept that purely tumour epithelium-centric metrics of aggressiveness may be incomplete and that incorporating markers of stromal ecology would improve prognosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
Nature ecology & evolution - 4(2020), 6 vom: 06. Juni, Seite 870-884 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Frankenstein, Ziv [VerfasserIn] |
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| Anmerkungen: |
Date Completed 24.08.2020 Date Revised 09.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41559-020-1157-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309770130 |
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| 520 | |a Prostate cancer (PCa) progression is a complex eco-evolutionary process driven by the feedback between evolving tumour cell phenotypes and microenvironmentally driven selection. To better understand this relationship, we used a multiscale mathematical model that integrates data from biology and pathology on the microenvironmental regulation of PCa cell behaviour. Our data indicate that the interactions between tumour cells and their environment shape the evolutionary dynamics of PCa cells and explain overall tumour aggressiveness. A key environmental determinant of this aggressiveness is the stromal ecology, which can be either inhibitory, highly reactive (supportive) or non-reactive (neutral). Our results show that stromal ecology correlates directly with tumour growth but inversely modulates tumour evolution. This suggests that aggressive, environmentally independent PCa may be a result of poor stromal ecology, supporting the concept that purely tumour epithelium-centric metrics of aggressiveness may be incomplete and that incorporating markers of stromal ecology would improve prognosis | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Franco, Omar E |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Javier, Rodrigo A |e verfasserin |4 aut | |
| 700 | 1 | |a Strand, Douglas W |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, MinJae |e verfasserin |4 aut | |
| 700 | 1 | |a Hayward, Simon W |e verfasserin |4 aut | |
| 700 | 1 | |a Ayala, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Alexander R A |e verfasserin |4 aut | |
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