Extracellular Vesicles and Metastasis.

Secretion of cell contents through extracellular vesicles (EVs), such as exosomes and microvesicles, is a fundamental cell behavior. Compared with their normal counterparts, cancer cells are different in the amount and composition of EVs they secrete as a result of intrinsic and extrinsic (microenvironmental) alterations. Although EVs were originally recognized as a means to remove undesired cell components, recent studies show their critical role in mediating intercellular interaction through cargo transport. In cancer, EVs can be transferred between different cancer cell subpopulations and between cancer and normal cells localized inside and outside of the tumor. By regulating various aspects of cellular functions, EVs contribute to tumor heterogeneity and plasticity, vascular remodeling, cancer-niche coevolution, immunomodulation, and establishment of premetastatic niche, all of which are important to the process of metastasis. Recent discoveries on EV-mediated mechanisms lead to a new understanding of the multifaceted changes in tumor and nontumor tissues before and after cancer metastasis, paving the way for new therapeutic strategies.