Figure 2.

Tumor-derived EVs in pre-metastatic niche (PMN) formation and tumorigenesis. Tumor-derived EVs express surface and cytosolic molecules originating from the primary tumor and are carried to recipient cell/organs via the circulation. The EV surface molecules and cargo confer pro-angiogenic, pro-migratory, pro-inflammatory effects, and chemotherapeutic drug interfering or immune-regulatory effects. EV movement to target organs is generally organotropic and determined by the inherent tumor cell and EV cargos. Finally, EVs contribute to the pre-conditioning of the target site via inducing extracellular matrix remodeling, changes in blood and lymphatic vessels barrier integrity, transfer of immune inhibitory or activating factors and transfer of oncogenic factors. Together these mechanisms explain EV contributions to cancer progression and the impact on cancer treatment efficacy including treatment failures.