Single cells must weaken or completely lose their adhesive bonds with neighboring tumor cells for infiltration, whereas collective migration requires stable cellCcell adhesion and multicellular coordinated movement (Friedl & Gilmour, 2009). accord and that has thus gained the ability to move through the extracellular matrix and penetrate basement membranes and endothelial walls upon intravasation and extravasation. These active migration mechanisms imply modification of cell morphology, position, and surrounding tissue (Friedl & Alexander, 2011). Furthermore, cancer cells may infiltrate as single entities, in clusters, in strands, or in single (Indian) files as observed in lobular breast carcinoma. Single cells must weaken or completely lose their adhesive bonds with neighboring tumor cells for infiltration, whereas collective Valdecoxib migration requires stable cellCcell adhesion and multicellular coordinated movement (Friedl & Gilmour, 2009). These clusters frequently comprise of different cell morphologies, that is, both epithelial-and mesenchymal-like. Collective migration may require a leader cell with mesenchymal features, able to create a path for the trailing tumor cells through the surrounding tissue (Friedl & Wolf, 2009). cancer cells are moved by external forces such as growth of the tumor, mechanical forces, or friction which cause them to be dragged or pushed out of place (Camara (Saucedo-Zeni (have also been used for the detection and molecular characterization of circulating tumor cells (Strati mRNA have also been found in a small number of healthy individuals (Stathopoulou mutations are known to block the effect of therapeutic EGFR IgG2b Isotype Control antibody (PE) inhibition by antibodies or small inhibitors in colorectal cancer patients (Wan mutation heterogeneity (i.e., and CTCs are present in the same patient) (Gasch wild-type primary colon carcinomas might be one explanation for failure of drug-mediated EGFR inhibition in these patients (Douillard mutations in colorectal cancer patients and the genomic heterogeneity of metastatic cellsthe actual targets of systemic therapyCis not taken into consideration for therapy decisions. In conclusion, the characterization of CTCs may have an important impact as companion diagnostics in future clinical trials testing new targeted therapies (Wan strategies to gain purity and enumeration of higher CTC counts. Clinically, quantification of CTCs is of high value as these cancer cells generally represent the tumor (metastases) and facilitate real-time monitoring during systemic therapies by sequential peripheral blood Valdecoxib sampling. Furthermore, molecular characterization of CTCs might enable the identification of therapeutic targets and contribute to personalized anti-metastatic therapies. Proof of the clinical relevance of the detection and characterization of CTCs has been substantially accumulating during the past decades. The use of xenograft models is a promising approach to gain further insights into the biology of tumor cell dissemination and may further help to test responses to newly designed therapies (Baccelli em et?al /em , 2013; Hodgkinson em et?al /em , 2014; Yu em et?al /em , 2014). In conclusion, analysis of CTCs in the peripheral blood (liquid biopsy) has a clear potential to further our understanding of the biology of tumor cell dissemination and to improve the management and possibly the prevention of metastatic disease in the near future. Conflict of interest The authors declare that they have no conflict of interest. Pending issues Do the currently used CTC enrichment and detection techniques allow us to Valdecoxib identify bona fide metastasis-initiating cells Valdecoxib (MICs)? Are EMT and MET required for tumor cell dissemination and metastasis outgrowth or are non-EMT events more effective in causing metastatic dissemination? Can CTCs be used to investigate the effectiveness of cancer treatment and are CTCs furthermore reliable targets to predict personalized treatment strategies based on a blood test (liquid biopsy)? Glossary CadherinsCalcium-dependent cell adhesion proteins involved in mechanisms regulating cellCcell adhesion, mobility, and proliferation of epithelial cells.CentromereA condensed and constricted region of a chromosome, to which the spindle fiber is attached during mitosis.ClaudinsImportant components of the tight junctions. Claudins are transmembrane proteins and establish the paracellular barrier, which controls the flow of molecules in the intercellular space between the cells of an epithelium.Circulating tumor cell (CTC)Cell that detached into the vasculature from a primary tumor or metastasis and can be found in the bloodstream of cancer patients.Disseminating tumor cell (DTC)Settlement of CTCs in secondary organs, such as liver, bone, and lungs. DTCs may stay in a dormant state or giving rise to an overt metastasis.Epithelial cell adhesion molecule (EpCAM)Cell adhesion molecule that is overexpressed in many carcinomas and.