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Figure 3. Extracellular vesicles and particles (EVPs) determine metastatic organotropism. Specific molecules expressed on EVPs interact with cells or the extracellular matrix of specific organs to deliver biomolecules to distant organs. This causes changes in the microenvironment, leading to pre-metastatic niche (PMN) formation and facilitating distant metastasis to specific organs. For example, tumor-derived EVPs expressing integrin αvβ5 are taken up by the liver and promote liver PMN formation. Similarly, integrin α6β1 and α6β4 expressed on tumor-derived EVPs are taken up by the lung and promote lung metastasis. Integrin α2β1 on cancer-associated fibroblast-derived EVPs also promotes lung metastasis. Integrin α5, miR-940, and miR-141-3p are involved in bone metastasis, CEMIP and miR-181c in brain metastasis, and integrin αv in lymph node metastasis, as reported. CDH11: cadherin 11; CEMIP: cell migration inducing hyaluronidase 1.