title: Midkine upregulates MICA/B expression in human gastric cancer cells and decreases natural killer cell cytotoxicity.
abstract: Midkine (MK) is a heparin-binding growth factor overexpressed in various human cancers. In the current study, a positive correlation was observed between MK expression and MICA/B serum levels of gastric cancer patients. In addition, MK transfection significantly increased MICA/B expression in gastric cancer cells. The soluble MICA/B expression was also elevated. Furthermore, MK transfection inhibited CD107a and Granzyme B expression, thereby suppressing the natural killer (NK) cell cytotoxicity in vitro. The phosphorylation of p38 MAPK and its promotion of CHOP expression were also observed after MK treatment and transfection. CHOP was indirectly bound to the MICA/B promoter region by interacting with AP-1, leading to MICA/B transcription. Overall, the current study shows that MK expression in tumor cells indirectly suppresses NK cytotoxicity by inducing MICA/B expression and suppressing NKG2D expression.
authors.affiliation: Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, People's Republic of China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Zhao
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Yunzhong
authors.initials: Y
authors.lastname: Nie
authors.forename: Qiongyu
authors.initials: Q
authors.lastname: Mi
authors.forename: Xingguo
authors.initials: X
authors.lastname: Chen
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D000078792:Midkine; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C497249:DDIT3 protein, human; D015395:Histocompatibility Antigens Class I; D052118:Lysosomal-Associated Membrane Protein 1; C066254:MDK protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009414:Nerve Growth Factors; D018808:Transcription Factor AP-1; D000078792:Midkine; D051742:Transcription Factor CHOP; D048051:p38 Mitogen-Activated Protein Kinases; D053804:Granzymes