Li Dongqi, Chu Xiangyu, Ma Yongsu, Zhang Fusheng, Tian Xiaodong, Yang Yanlian, Yang Yinmo
Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China.
Cancer Lett. 2024 Dec 19;611:217403. doi: 10.1016/j.canlet.2024.217403.
Pancreatic cancer (PC) is one of the most malignant solid cancers, and PC metastasis, particularly liver metastasis, is a major cause of cancer mortality. A key event in tumor metastasis is the formation of pre-metastatic niche (PMN), which provides a microenvironment conducive to tumor cells colonization and progression. Various molecules loaded in tumor-derived exosomes (TDEs) contribute to PMN formation and distant tumor metastasis, by regulating immune and stromal cell function, inducing angiogenesis, and promoting metabolic reprogramming. Therefore, therapies targeting PMN may offer novel advantages to prevent tumor metastasis at an earlier stage. In this review, we summarize multifaceted mechanisms underlying hepatic PMN formation, with a focus on how PC TDEs participate in angiogenesis and vascular permeability, create immune suppressive microenvironment, remodel the extracellular matrix, and regulate metabolic reprogramming. In addition, we highlight the promise of TDEs for early diagnosis and effective therapy of PC liver metastases.
胰腺癌（PC）是最具侵袭性的实体癌之一，而PC转移，尤其是肝转移，是癌症死亡的主要原因。肿瘤转移中的一个关键事件是前转移生态位（PMN）的形成，它为肿瘤细胞的定植和进展提供了有利的微环境。肿瘤来源外泌体（TDEs）中装载的各种分子通过调节免疫和基质细胞功能、诱导血管生成和促进代谢重编程，有助于PMN的形成和远处肿瘤转移。因此，针对PMN的治疗可能在更早阶段预防肿瘤转移方面具有新的优势。在这篇综述中，我们总结了肝PMN形成的多方面机制，重点关注PC TDEs如何参与血管生成和血管通透性、创建免疫抑制微环境、重塑细胞外基质以及调节代谢重编程。此外，我们强调了TDEs在PC肝转移早期诊断和有效治疗方面的前景。
