TDEVs carry soluble protein factors that influence the local ECM and stromal cells, contributing to the development of premetastatic niche conditions in target organs.106 Abnormal remodeling of the ECM, caused by tumor invasion, alters the characteristics of cancer cells by increasing matrix stiffness and providing substrates for their migration.252,253 ECM factors such as fibronectin, tenascin, periostin, and versican are involved in premetastatic niche formation. The gene discussed is FN1; the disease is cancer.