Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis. This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy. This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.

中文翻译：

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揭示癌症相关成纤维细胞在肿瘤转移中的关键作用：机制和治疗前景


肿瘤转移代表逐步进展，是癌症患者不良预后的主要决定因素。因此，深入探讨其机制具有重要的临床意义。癌症相关成纤维细胞（CAF）是肿瘤微环境（TME）中最丰富的基质细胞群，其在肿瘤转移中的关键调节作用已获得强有力的证据支持。本综述系统地探讨了 CAF 在致瘤传播的八个关键阶段的作用：1) 细胞外基质 (ECM) 重塑，2) 上皮间质转化 (EMT)，3) 血管生成，4) 肿瘤代谢，5) 血管周围迁移，6 ) 免疫逃逸，7) 休眠，以及 8) 转移前生态位 (PMN) 形成。此外，我们还提供了旨在癌症治疗中针对 CAF 的现有策略概要。这篇综述描绘了 CAF 与肿瘤转移之间相互作用的结构化框架，同时为潜在的治疗发展提供了见解。它有助于更​​深入地了解 TME 内的癌症转移，促进 CAF 靶向疗法在抗转移方法中的应用。