Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Canada 200 College St., Toronto, ON, M5S 3E5, Canada.
Br J Cancer. 2020 Mar;122(7):931-942. doi: 10.1038/s41416-019-0705-1. Epub 2020 Jan 29.
The tumour microenvironment (TME) determines vital aspects of tumour development, such as tumour growth, metastases and response to therapy. Cancer-associated fibroblasts (CAFs) are abundant and extremely influential in this process and interact with cellular and matrix TME constituents such as endothelial and immune cells and collagens, fibronectin and elastin, respectively. However, CAFs are also the recipients of signals-both chemical and physical-that are generated by the TME, and their phenotype effectively evolves alongside the tumour mass during tumour progression. Amid a rising clinical interest in CAFs as a crucial force for disease progression, this review aims to contextualise the CAF phenotype using the chronological framework of the CAF life cycle within the evolving tumour stroma, ranging from quiescent fibroblasts to highly proliferative and secretory CAFs. The emergence, properties and clinical implications of CAF activation are discussed, as well as research strategies used to characterise CAFs and current clinical efforts to alter CAF function as a therapeutic strategy.
肿瘤微环境（TME）决定了肿瘤发展的重要方面，如肿瘤生长、转移和对治疗的反应。癌症相关成纤维细胞（CAFs）在这个过程中丰富且极具影响力，分别与细胞和基质 TME 成分如内皮细胞和免疫细胞以及胶原蛋白、纤维连接蛋白和弹性蛋白相互作用。然而，CAFs 也是 TME 产生的信号的接受者，包括化学和物理信号，并且它们的表型在肿瘤进展过程中伴随着肿瘤块的变化而有效进化。在临床对 CAFs 作为疾病进展的关键力量的兴趣日益增加的情况下，本综述旨在使用 CAF 生命周期的时间框架，根据不断演变的肿瘤基质，将 CAF 表型置于背景中，范围从静止的成纤维细胞到高度增殖和分泌的 CAFs。讨论了 CAF 激活的出现、特性和临床意义，以及用于表征 CAFs 的研究策略和当前改变 CAF 功能作为治疗策略的临床努力。
