Department of Surgery, NorthShore University HealthSystem, Research Institute, 1001 University Place, Evanston, IL, 60201, USA.
Department of Surgery, NorthShore University HealthSystem, Research Institute, 1001 University Place, Evanston, IL, 60201, USA. Electronic address: http://
Cancer Lett. 2022 Jan 28;525:76-83. doi: 10.1016/j.canlet.2021.10.028. Epub 2021 Oct 29.
Our understanding of stromal components, specifically cancer-associated fibroblasts (CAF), in prostate cancer (PCa), has evolved from considering these cells as inert bystanders to acknowledging their significance as players in prostate tumorigenesis. CAF are multifaceted-they promote cancer cell growth, migration and remodel the tumor microenvironment. Although targeting CAF could be a promising strategy for PCa treatment, they incorporate a high but undefined degree of intrinsic cellular heterogeneity. The interaction between CAF subpopulations, with the normal and tumor epithelium and with other cell types is not yet characterized. Defining these interactions and the critical signaling nodes that support tumorigenesis will enable the development of novel strategies to control prostate cancer progression. Here we will discuss the origins, molecular and functional heterogeneity of CAF in PCa. We highlight the challenges associated with delineating CAF heterogeneity and discuss potential areas of research that would assist in expanding our knowledge of CAF and their role in PCa tumorigenesis.
我们对前列腺癌(PCa)中基质成分(特别是癌相关成纤维细胞 [CAF])的理解已经从将这些细胞视为无活性的旁观者转变为承认它们在前列腺肿瘤发生中的重要作用。CAF 具有多面性——它们促进癌细胞生长、迁移并重塑肿瘤微环境。尽管靶向 CAF 可能是治疗 PCa 的一种有前途的策略,但它们包含高度但定义不明确的内在细胞异质性。CAF 亚群与正常和肿瘤上皮以及与其他细胞类型之间的相互作用尚未得到描述。定义这些相互作用以及支持肿瘤发生的关键信号节点将能够开发控制前列腺癌进展的新策略。在这里,我们将讨论 PCa 中 CAF 的起源、分子和功能异质性。我们强调了描绘 CAF 异质性相关的挑战,并讨论了潜在的研究领域,这将有助于扩展我们对 CAF 及其在 PCa 肿瘤发生中的作用的认识。