Suppression of anchorage-independent growth of human glioblastoma cell by major histocompatibility complex class I gene-transfection.

Abstract

The host's immune system discriminates tumor cells from normal cells by recognizing the major histocompatibility complex (MHC) class I antigen expressed on the tumor cell membrane. However, the role of MHC class I antigen in tumor cells has not yet been clarified. In this study, the influence of MHC class I antigen expression on the tumorigenicity of a human glioblastoma cell line (KMG4) is examined. Barely detectable levels of MHC class I messenger ribonucleic acid were found to express in KMG4 cells by Northern blot analysis using mouse MHC class I (H-2Ld) and human leukocyte antigen (HLA)-B7 genes as probes. The H-2Ld gene connected at the downstream end of murine mammary tumor virus (MMTV)-promoter was cotransfected with the neomycine-resistant gene pSV2-neo into KMG4 cells, and the drug-resistant cells were selected. The KMG4 cells (KMG4-MMTV-Ld), which acquired the MHC class I gene were detected by Northern blot analysis with H-2Ld as the probe, and by immunohistochemistry using the H-2Ld-specific monoclonal antibody. Tumorigenicity, as determined by colony-forming ability in soft agar, was then compared between MHC class I-expressing KMG4-MMTV-Ld and nonexpressing control cells. The MHC class I-expressing cells were found to be deprived of colony-forming ability, indicating that MHC class I antigen could negatively influence the anchorage-independent cell growth of the human glioblastoma cell line KMG4.