Figure 1.

Schematic representation of circulating tumor cells (CTCs) detaching from primary tumor, intravasating into the bloodstream, and circulating to colonize distant organs after extravasating where they create secondary metastasis. Essentially, CTCs undergo epithelial-to-mesenchymal transmission (EMT), where cancerous epithelial cells lose their cell-to-cell contact and develop a more motile and less differentiated mesenchymal phenotype. In addition, infiltrating protumor neutrophils secrete proteolytic enzyme (e.g., matrix metallopeptidase 9 (MMP-9)) to aid CTCs in entering the bloodstream. In the bloodstream, these disseminating cells must overcome blood shear stress, anoikis and immune system response. Once reaching the distant cite, CTCs revert back to their epithelial phenotype and grow into secondary metastasis. CTCs can exist in the form of single cells or cell clusters which has increased metastatic potential. CTCs encompass more of the clonal populations in a tumor, they give a complete picture of tumor composition and how it changes overtime. They can be distinguished from other types of cells circulating in the blood through their differential expression of EMT biomarkers such as epithelial cell adhesion molecules (EpCAM) and Cytokeratin (CK).