Lodha Pragati, Acari Alperen, Rieck Jochen, Hofmann Sarah, Dieterich Lothar C
European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Cancers (Basel). 2024 Dec 2;16(23):4039. doi: 10.3390/cancers16234039.
Tumor growth and progression require molecular interactions between malignant and host cells. In recent years, extracellular vesicles (EVs) emerged as an important pillar of such interactions, carrying molecular information from their donor cells to distant recipient cells. Thereby, the phenotype and function of the recipient cells are altered, which may facilitate tumor immune escape and tumor metastasis to other organs through the formation of pre-metastatic niches. A prerequisite for these effects of tumor cell-derived EVs is an efficient transport system from the site of origin to the body periphery. Here, we highlight the role of the lymphatic vascular system in the distribution and progression-promoting functions of tumor cell-derived EVs. Importantly, the lymphatic vascular system is the primary drainage system for interstitial fluid and its soluble, particulate, and cellular contents, and therefore represents the principal route for regional (i.e., to tumor-draining lymph nodes) and systemic distribution of EVs derived from solid tumors. Furthermore, recent studies highlighted the tumor-draining lymph node as a crucial site where tumor-derived EVs exert their effects. A deeper mechanistic understanding of how EVs gain access to the lymphatic vasculature, how they interact with their recipient cells in tumor-draining lymph nodes and beyond, and how they induce phenotypic and functional maladaptation will be instrumental to identify new molecular targets and conceive innovative approaches for cancer therapy.
肿瘤的生长和进展需要恶性细胞与宿主细胞之间的分子相互作用。近年来，细胞外囊泡（EVs）成为这种相互作用的重要支柱，将分子信息从其供体细胞传递到远处的受体细胞。由此，受体细胞的表型和功能发生改变，这可能通过形成前转移微环境促进肿瘤免疫逃逸和肿瘤转移至其他器官。肿瘤细胞衍生的EVs产生这些效应的一个先决条件是从起源部位到身体外周的高效运输系统。在此，我们强调淋巴管系统在肿瘤细胞衍生的EVs的分布和促进进展功能中的作用。重要的是，淋巴管系统是组织液及其可溶性、颗粒性和细胞成分的主要引流系统，因此是实体瘤衍生的EVs进行区域（即至肿瘤引流淋巴结）和全身分布的主要途径。此外，最近的研究强调肿瘤引流淋巴结是肿瘤衍生的EVs发挥作用的关键部位。更深入地了解EVs如何进入淋巴管系统、它们如何在肿瘤引流淋巴结及其他部位与其受体细胞相互作用，以及它们如何诱导表型和功能失调，将有助于识别新的分子靶点并构思创新的癌症治疗方法。
