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.

中文翻译：

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基质反应性不同地驱动肿瘤细胞进化和前列腺癌进展。


前列腺癌（PCa）的进展是一个复杂的生态进化过程，由不断进化的肿瘤细胞表型和微环境驱动的选择之间的反馈驱动。为了更好地理解这种关系，我们使用了多尺度数学模型，该模型整合了有关 PCa 细胞行为微环境调节的生物学和病理学数据。我们的数据表明，肿瘤细胞与其环境之间的相互作用塑造了 PCa 细胞的进化动力学，并解释了肿瘤的整体侵袭性。这种攻击性的一个关键环境决定因素是基质生态，它可以是抑制性的、高反应性的（支持性的）或非反应性的（中性的）。我们的结果表明，基质生态与肿瘤生长直接相关，但反向调节肿瘤进化。这表明侵袭性、与环境无关的PCa可能是基质生态不良的结果，支持了这样的概念：纯粹以肿瘤上皮为中心的侵袭性指标可能是不完整的，并且结合基质生态学标志物将改善预后。