Open AccessEpithelial‐mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1
Author(s) -
Hu Baoguang,
Tian Xiaokun,
Li Yanbin,
Liu Yangchun,
Yang Tao,
Han Zhaodong,
An Jiajia,
Kong Lingqun,
Li Yuming
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2871
Subject(s) - circulating tumor cell , epithelial–mesenchymal transition , cancer research , immune system , biology , nkg2d , cancer , mesenchymal stem cell , metastasis , immunology , cytotoxic t cell , microbiology and biotechnology , in vitro , biochemistry , genetics
Background 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 increasing cell survival and early colonization. However, the exact role of EMT in CTCs remains unclear. Methods In this study, we identified CTCs 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 ULBP1 (a major member of the NKG2D—natural killer [NK] group 2 member D—ligand family) on CTCs. Moreover, we investigated the relationship between the expression of EMT markers and ULBP1 on CTCs and gastric cancer cell lines. Results Our results showed that the CTCs of gastric cancer patients exhibited three EMT marker subtypes, and that the expression of ULBP1 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 ULBP1. Conclusions Our study indicated that EMT might play a vital role in the immune invasion of CTCs by regulating the expression of ULBP1 on CTCs. These findings could provide potential strategies for targeting the immune evasion capacity of CTCs.