RRC ID 65472
Author Garrido-Tapia M, Hernández CJ, Ascui G, Kramm K, Morales M, Ga Rate V, Zúñiga R, Bustamante M, Aguillón JC, Catala N D, Ribeiro CH, Molina MAC.
Title STAT3 inhibition by STA21 increases cell surface expression of MICB and the release of soluble MICB by gastric adenocarcinoma cells.
Journal Immunobiology
Abstract NKG2D is an activating receptor expressed on NK cells that binds to a variety of ligands, including MICA and MICB. These cell surface glycoproteins are overexpressed under cellular transformation, thus playing an important role in cell-mediated immune response to tumors. STAT3 is a transcription factor that is constitutively active in cancer. It negatively regulates MICA expression on target cells, while its inhibition enhances NK cell cytotoxicity against tumors. In this work, we aimed to describe the effect of STAT3 signaling inhibition by STA21 on the regulation of MICB expression in gastric adenocarcinoma cells and its effect on the cytotoxic function of NK cells. Treatment of gastric adenocarcinoma cells with STA21 induced an increase in MICB expression and soluble MICB secretion, as well as a variable pattern on effector cell degranulation. Soluble MICB secretion by gastric adenocarcinoma cells was not affected by metalloprotease inhibition. We also observed that primary gastric adenocarcinoma tissue released soluble MICB into the extracellular milieu. Recombinant MICB induced a significant decrease in the levels of NKG2D receptor on effector NK and CD8+ T cells, which correlated with an impaired cytotoxic function. Altogether, our data provide evidence that STAT3 signaling pathway regulates MICB expression on gastric adenocarcinoma cells and that recombinant soluble MICB compromises the cytolytic activity of NK cells.
Volume 222(11)
Pages 1043-1051
Published 2017-11-1
DOI 10.1016/j.imbio.2017.05.009
PII S0171-2985(17)30091-8
PMID 28578917
MeSH Adenocarcinoma / drug therapy* Adenocarcinoma / genetics CD8-Positive T-Lymphocytes / immunology* Cell Degranulation Cells, Cultured Cytotoxicity, Immunologic Gene Expression Regulation / drug effects Histocompatibility Antigens Class I / genetics Histocompatibility Antigens Class I / metabolism* Humans Killer Cells, Natural / immunology* NK Cell Lectin-Like Receptor Subfamily K / metabolism Polycyclic Compounds / pharmacology STAT3 Transcription Factor / metabolism* Signal Transduction Stomach Neoplasms / drug therapy* Stomach Neoplasms / genetics
IF 2.788
Human and Animal Cells MKN45(RCB1001)