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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:机制与治疗前景

Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.

作者信息

Liu Yingxue, Zhang Xiaoyan, Gu Wenchao, Su Hui, Wang Xin, Wang Xu, Zhang Jiayu, Xu Midie, Sheng Weiqi

机构信息

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China.

Department of Diagnostic and Interventional Radiology, University of Tsukuba, Ibaraki, Japan.

出版信息

J Adv Res. 2025 May;71:399-413. doi: 10.1016/j.jare.2024.05.031. Epub 2024 May 31.

Abstract

BACKGROUND

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.

AIM OF REVIEW

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.

KEY SCIENTIFIC CONCEPTS OF REVIEW

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.

摘要

背景

肿瘤转移是一个逐步发展的过程,是癌症患者预后不良的主要决定因素。因此,深入探究其机制具有至关重要的临床意义。癌症相关成纤维细胞(CAFs)是肿瘤微环境(TME)中最丰富的基质细胞群体,已有充分证据支持其在肿瘤转移中起关键调节作用。

综述目的

本综述系统探讨了CAFs在肿瘤发生扩散的八个关键阶段所起的作用: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;8)前转移微环境(PMN)形成。此外,我们还汇总了目前在癌症治疗中针对CAFs的策略。

综述的关键科学概念

本综述勾勒了CAFs与肿瘤转移之间相互作用的结构化框架,同时为潜在的治疗进展提供了见解。它有助于更深入地理解TME内的癌症转移,促进在抗转移方法中利用靶向CAF的疗法。

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