WITHDRAWN: Epithelial-mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of NKG2D ligands

Abstract

Increasing numbers of studies have demonstrated that circulating tumor cells (CTCs) undergo a phenotypic change termed epithelial-mesenchymal transition (EMT), and researchers have proposed that EMT might provide CTCs with increased potential to survive in the different microenvironments encountered during metastasis through various ways, such as by enhancing metastatic competence, and increasing cell survival and early colonization. However, the exact role of EMT in CTCs remains unclear. In this study, we identified CTCs in the peripheral blood of 41 patients with gastric cancer using Cyttel-CTC and im-FISH (immune-fluorescence in situ hybridization) methods, and tested the expression of EMT markers and NK-cell receptor D (NKG2D) ligands on CTCs. Moreover, we investigated the relationship between the expression of EMT markers and NKG2D ligands on CTCs and gastric cancer cell lines. The results showed that the CTCs in the peripheral blood of gastric cancer patients exhibited three EMT marker subtypes, and that the expression of NKG2D ligands was significantly lower on mesenchymal phenotypic CTCs (M + CTCs) than on epithelial phenotypic CTCs (E + CTCs). EMT induced by TGF-β in vitro produced a similar phenomenon, and we therefore proposed that EMT might be involved in the immune evasion of CTCs from NK cells by altering the expression of NKG2D ligands. In conclusion, our study indicated that EMT might play a key role in the immune invasion of gastric CTCs by regulating the expression of NKG2D ligands on the tumor cells. These findings could provide potential strategies for targeting the immune evasion capacity of CTCs.