The CSC concept of cancer proposes that tumor developmentand progression is driven by a small subpopulation of cells within the tumor, termed CSCs, which possess the potential for unlimitedself-renewal [11]. CSCs display a phenotype similar to embryonicstem cells (ESCs) [4] and have been identified in a range of cancersincluding pancreatic cancer [12], oral cavity squamous cell carcinoma(OCSCC) [13], and colorectal cancer [14]. Their existenceand their role in initiating cancer makes CSCs a novel therapeutictarget. Metastases also show the presence of CSCs, including livermetastases from colon adenocarcinoma [15], metastatic pancreaticcancer [16], and metastatic breast cancer [17], suggesting thatthese CSCs have the ability to migrate from the primary tumor,using a major physiological ‘highway’, such as the bloodstreamor lymph system, to seed at distant sites, although clinical metastasisis rarely observed in GB, possibly due to the short life expectancyof the patients.Circulating tumor stem cells (CTSCs) present an alternative toinvasive biopsies as a means of detecting, characterizing and monitoringdisease [18]. CTSCs are shed from the primary tumor and/ora metastatic lesion into the vasculature and/or lymphatic channels[19] and subsequently initiate metastatic growth [20]. CTSCs havebeen identified in many cancer types including colon [21], lung[22], and breast [23] cancer. Underscored by the CSC concept, thesecells possess the means of initiating tumorigenesis, therefore theirability to disseminate from the parent lesion into the circulationand seed within the organ of origin or at distant organs, could befundamental to local recurrence or the classically accepted distanthematogenous metastasis [19,24,25].An important initiating step of metastasis is epithelial-tomesenchymaltransition (EMT) [24–26], in which a polarizedepithelial cell assumes a mesenchymal, more immature phenotype,increasing its migratory capacity and invasiveness [27]. CTSCs displayingmarkers of EMT have been identified in metastatic cancers[26], and there have also been links between the biological mechanismsoperating in CSCs and EMT, suggesting that EMT and its associatedprocesses play a key role in tumorigenesis [28].