Stromal reactivity differentially drives tumour cell evolution and prostate cancer progression

Ziv Frankenstein, David Basanta, Omar E. Franco, Yan Gao, Rodrigo A. Javier, Douglas W. Strand, Min Jae Lee, Simon W. Hayward, Gustavo Ayala, Alexander R.A. Anderson

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)870-884
Number of pages15
JournalNature Ecology and Evolution
Volume4
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Ecology

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