In this study, we have investigated if current cancer therapeutic modalities including hyperthermia and ionizing radiation can increase the expression of NKG2D ligands in human cancer cell lines. The expressions of NKG2D ligands were induced by both heat shock and ionizing radiation in various cell lines including KM12, NCI-H23, HeLa and A375 cells with peaks at 2 h and 9 h after treatment, respectively, although inducibility of each NKG2D ligand was various depending on cell lines. During the induction of NKG2D ligands, heat shock protein 70 was induced by heat shock but not by ionizing radiation. These results were followed by increased susceptibilities to NK cell-mediated cytolysis after treatment with heat shock and ionizing radiation. These results suggest that heat shock and ionizing radiation induce NKG2D ligands and consequently might lead to increased NK cell-mediated cytotoxicity in various cancer cells.
The abilities of NKG2D ligands to specifically mark stressed or transformed cells and activate NK cells suggest the possibility that the expression levels of NKG2D ligands in cancers may be helpful to predict the efficacy of NK cell-based cancer immunotherapy. Therefore, a multiplex RT-PCR was developed and used for rapid and simultaneous analysis of the expression level of NKG2D ligands in cancer cells and tissues. With total RNAs isolated from various cancer cell lines, the multiplex RT-PCR revealed various expression patterns of NKG2D ligands. With total tissue RNAs, the gastrointestinal tumors showed consistently increased NKG2D ligands, compared with adjacent normal tissues. However, NKG2D ligands were not always consistently increased in tumor tissues and expression patterns of NKG2D ligands were heterogeneous between patients, especially in breast and lung cancers. In addition, expression patterns of NKG2D ligands were very similar between various paired primary and their multidrug-resistant/metastatic cells, except MCF-7 sublines. These results demonstrated that the multiplex RT-PCR might be a useful diagnostics to detect the expression levels of NKG2D ligands in tissues as well as cells, and suggested that the gastrointestinal tumors might be good candidates for NK cell-based cancer immunotherapy, since it showed significantly higher levels of NKG2D ligands than adjacent normal tissues.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.