Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon.
To elicit a tumor immune response, tumor antigens represented by major histocompatibility (MHC) class I complex on the cell surface is indispensable. Some investigators demonstrated that many cancer cells reduce expression of beta2-microglobulin, a transporter of antigen presenting (TAP) or low molecular protein (LMP), due to the deletion mutant or point mutation. We investigated gene expression levels of antigen presenting machineries in 13 cell lines of the pancreas, biliary tract and colon cancer by using real-time quantitative PCR. We also evaluated the correlation between expression of MHC class I and that of antigen-processing molecules in these gastrointestinal cancer cell lines. Flow cytometric analysis showed that expression of MHC class I for the pancreatic cancer cell lines was generally lower than that for the biliary tract or colon cancer cell lines. It was further found that the colon cancer cell lines HCT-15/DLD-1 showed no MHC class I expression and lack of protein expression for beta2-microglobulin. Transfection of the wild-type beta2-microglobulin gene restored MHC class I antigen expression on the cell surface for DLD-1. Quantitative real-time PCR demonstrated lower expression for TAP1, TAP2, LMP2 and LMP7 gene in five cancer cell lines. Partial correlation analysis demonstrated that LMP2 was the only antigen presenting machinery which was significantly associated with MHC class I expression. Our results suggest that beta2-microglobulin and LMP2 are important for the expression of MHC class I in 13 gastrointestinal cancer cell lines, while the combined but complex expression of antigen presenting mechanisms was related to MHC class I expression level on the surface of cancer cells.
Imanishi
Tatsuya
T
Division of Gastrointestinal Surgery, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Kamigaki
Takashi
T
Nakamura
Tetsu
T
Hayashi
Shun
S
Yasuda
Takashi
T
Kawasaki
Kentaro
K
Takase
Shiro
S
Ajiki
Tetsuo
T
Kuroda
Yoshikazu
Y
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D017951:Antigen Presentation / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000378:metabolism*; D001661:Biliary Tract Neoplasms / Q000235:genetics / Q000276:immunology; D002277:Carcinoma / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000235:genetics; D004067:Digestive System Neoplasms / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology; D014162:Transfection; D001613:beta 2-Microglobulin / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; C477327:transporter associated with antigen processing (TAP); C071313:LMP-2 protein; D003546:Cysteine Endopeptidases