Figure 2.

Metastasis includes five steps: local invasion, intravasation, hematogenous survival and transport, extravasation and colonization. EMT is a multistep transitional process that produces epithelial, mesenchymal and hybrid CTCs. Tumor cells may actively or passively enter the bloodstream via EMT or other biological events. In the circulation, CTCs may overcome several hurdles including shear forces, anoikis, and immune defense. After survival in the bloodstream, CTCs may move under the collisions with other blood cells and be recruited to the vascular walls, allowing them to transmigrate through the endothelium. At the distant site, CTCs may extravasate and undergo MET, which enables the colonization of CTCs and ultimately results in metastatic lesions.