Fig. 2

Metastatic cascade. a Acquisition of metastatic potential via epithelial-mesenchymal transition, degradation of the ECM (secretion of MMPs) and invasion through the basement membrane. Immune cells are recruited to the primary tumor site via cancer cell-derived and CAF-derived factors and cytokines. b Intravasation of cancer cells via invadopodia formation. Cancer cells acquire the resistance to anoikis. c Survival in the circulation. Cancer cells mediate the so-called tumor cell-induced platelet aggregation (TCIPA) to form a “platelet cloak” in order to be protected from TNF-α and to escape NK cells. Cancer cells evade the immune system by upregulation of indoleamine 2,3-dioxygenase (IDO). d Extravasation and formation of a secondary tumor site. Arrest of tumor cells on the endothelium, sequestration of tumor cells via NET formation, followed by transendothelial migration and invasion into the surrounding tissue. Abbreviations: TAM tumor-associated macrophage, TAN tumor-associated neutrophil, MDSC myeloid-derived suppressor cell, NK natural killer cell, Treg regulatory T cell, CAF cancer-associated fibroblast, ECM extracellular matrix, MMPs matrix metalloproteinases, MIF migration inhibitory factor, TGF-β transforming growth factor-β, EGF epithelial growth factor, HGF hepapocyte growth factor, TNF- α tumor necrosis factor-α, IDO indoleamine 2,3-dioxygenase, NET neutrophil extracellular trap