Fig. 3

Role of EMT in the tumor metastasis. Tumor cells in situ are induced by EMT to initiate the metastatic cascade process. Intermediate state and mesenchymal stem cells (MCSCs) lose intercellular junctions, detach from tumor tissue, and invade surrounding tissues. Metastatic tumor cells enter the circulation through the endothelial barrier by active or passive trans-endothelial migration (TEM), invading the surrounding mesenchyme and disrupting endothelial junctions. After entering the circulation, single or clustered circulating tumor cells (CTCs) can bind to coagulation factors on platelets by expressing thrombin, forming a unique immune mechanism that protects metastatic cells from immune escape. Neutrophils are also recruited and bind to CTCs to promote tumor cells survival and proliferation. CTCs move slowly, roll along the endothelium, and then arrest. MCSCs anchor with endothelial cells for extravasation and then colonize distal organs via the MET process