Figure 1, Key Figure. Multiple parallel pathways for cancer cell dissemination from a primary tumor.

Key steps in the metastatic cascade - intravasation, circulation, extravasation- often exhibit parallel routes. Characteristics of the tumor vasculature and the role of the immune system dictate the mechanism of dissemination and the transition of tumor cells from different microenvironments and states. Cancer cells at the primary site may encounter intact or partially lined vasculature, which may affect the mode of intravasation (i.e. single cells or microemboli). Microemboli exhibit shorter half-lives in circulation than single tumor cells and interact to a larger degree with blood constituents. These interactions determine the mode of arrest in downstream vessels (i.e. rolling adhesion or vessel occlusion) and organs, and ultimately impact extravasation and possibly dormancy and/or extravascular growth. Supporting clinical and pre-clinical evidence for the transition of tumor cells between states is represented by the dashed or solid lines, respectively.