Extracellular Vesicles: Hermes between cancers and lymph nodes.

Cancer is one of the main causes of death and a major obstacle to increasing life expectancy in all countries of the world. Lymph node metastasis (LNM) of in cancer patients indicates poor prognosis and it is an important indication to determine the therapeutic regime. Therefore, more attention should be given to the molecular mechanics of tumor lymphangiogenesis and LNM. Extracellular vesicles (EVs) are nanoscale cargo-bearing membrane vesicles that can serve as key mediators for the intercellular communication. Like Hermes, the messenger of the Greek gods, EVs can be secreted by tumor cells to regulate the LNM process. Many evidence has proved the clinical correlation between EVs and LNM in various cancer types. EVs plays an active role in the process of metastasis by expressing its connotative molecules, including proteins, nucleic acids, and metabolites. However, the clear role of EVs in the process of cancer LNM has not been thoroughly studied yet. In this review, we will summarize the clinical and mechanical findings of EVs regulating role on cancer LNM, and discuss the advanced modification of the research proposal. We propose the "PUMP" principle of EVs in LNM, including Preparation, Unleash, Migration, and Planting.