**4.3. Missing data: implication of gastric cancer stem cells in metastasis?**

Another important property of CSCs is their ability to initiate metastasis. Metastasis is a rare event [79] requiring the acquisition of invasive properties through epithelial-mesenchymal transition (1) to escape from the niche of the primary tumor in order to disseminate to distant organs after extravasation as circulating tumor cells (CTCs) and (2) to initiate secondary tumors [80]. We reported that the CD44<sup>+</sup> cells with CSC-like properties induced by *H. pylori* infection but not the CD44− cells overexpressed mesenchymal markers such as Vimentin and Zeb1 and downregulated epithelial markers and tumorigenic, migratory, and invasive properties [36, 81]. Chen et al. identified CTCs characterized by CD44<sup>+</sup> CD54<sup>+</sup> expression in the peripheral blood from patients with gastric cancer which were able to form tumorspheres and generate heterogeneous tumors when injected into immunodeficient mice; these CTCs had a self-renewal capability both in cell culture and in mouse models [82]. This study suggested that CD44<sup>+</sup> CD54<sup>+</sup> CTCs could represent metastatic GCSCs. Nevertheless, the characterization of the CSC subpopulation capable of initiating metastases needs to be determined.
