{"title":"转移前生态位:形成、特征和治疗意义","authors":"Yuhang Wang, Jiachi Jia, Fuqi Wang, Yingshuai Fang, Yabing Yang, Quanbo Zhou, Weitang Yuan, Xiaoming Gu, Junhong Hu, Shuaixi Yang","doi":"10.1038/s41392-024-01937-7","DOIUrl":null,"url":null,"abstract":"<p>Distant metastasis is a primary cause of mortality and contributes to poor surgical outcomes in cancer patients. Before the development of organ-specific metastasis, the formation of a pre-metastatic niche is pivotal in promoting the spread of cancer cells. This review delves into the intricate landscape of the pre-metastatic niche, focusing on the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The discussion encompasses cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells, in addition to molecular factors like secreted substances from tumors and extracellular vesicles, within the framework of pre-metastatic niche formation. Insights into the temporal mechanisms of pre-metastatic niche formation such as epithelial-mesenchymal transition, immunosuppression, extracellular matrix remodeling, metabolic reprogramming, vascular permeability and angiogenesis are provided. Furthermore, the landscape of pre-metastatic niche in different metastatic organs like lymph nodes, lungs, liver, brain, and bones is elucidated. Therapeutic approaches targeting the cellular and molecular components of pre-metastatic niche, as well as interventions targeting signaling pathways such as the TGF-β, VEGF, and MET pathways, are highlighted. 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引用次数: 0
摘要
远处转移是癌症患者死亡的主要原因,也是手术效果不佳的原因之一。在发生器官特异性转移之前,转移前生态位的形成是促进癌细胞扩散的关键。本综述深入探讨了转移前生态位的复杂情况,重点关注肿瘤分泌因子、细胞外囊泡和循环肿瘤细胞在形成转移生态位中的作用。除了肿瘤分泌物质和细胞外囊泡等分子因素外,讨论还将巨噬细胞、中性粒细胞、骨髓抑制细胞和T/B细胞等细胞因素纳入转移前生态位形成的框架。研究还深入探讨了转移前生态位形成的时间机制,如上皮-间质转化、免疫抑制、细胞外基质重塑、代谢重编程、血管通透性和血管生成。此外,还阐明了淋巴结、肺、肝、脑和骨骼等不同转移器官中转移前生态位的情况。重点介绍了针对转移前生态位的细胞和分子成分的治疗方法,以及针对 TGF-β、血管内皮生长因子和 MET 通路等信号通路的干预措施。本综述旨在加深我们对转移前生态位动态的了解,并为制定有效的治疗策略以对抗肿瘤转移提供见解。
Pre-metastatic niche: formation, characteristics and therapeutic implication
Distant metastasis is a primary cause of mortality and contributes to poor surgical outcomes in cancer patients. Before the development of organ-specific metastasis, the formation of a pre-metastatic niche is pivotal in promoting the spread of cancer cells. This review delves into the intricate landscape of the pre-metastatic niche, focusing on the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The discussion encompasses cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells, in addition to molecular factors like secreted substances from tumors and extracellular vesicles, within the framework of pre-metastatic niche formation. Insights into the temporal mechanisms of pre-metastatic niche formation such as epithelial-mesenchymal transition, immunosuppression, extracellular matrix remodeling, metabolic reprogramming, vascular permeability and angiogenesis are provided. Furthermore, the landscape of pre-metastatic niche in different metastatic organs like lymph nodes, lungs, liver, brain, and bones is elucidated. Therapeutic approaches targeting the cellular and molecular components of pre-metastatic niche, as well as interventions targeting signaling pathways such as the TGF-β, VEGF, and MET pathways, are highlighted. This review aims to enhance our understanding of pre-metastatic niche dynamics and provide insights for developing effective therapeutic strategies to combat tumor metastasis.
期刊介绍:
Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy.
Scope: The journal covers research on major human diseases, including, but not limited to:
Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.