DKK3 attenuates the cytotoxic effect of natural killer cells on CD133+ gastric cancer cells

Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem‐like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells re...

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Bibliographic Details
Published in:Molecular carcinogenesis 2017-07, Vol.56 (7), p.1712-1721
Main Authors: Xia, Pu, Xu, Xiao‐Yan
Format: Article
Language:English
Subjects:
AC133 Antigen - genetics
AC133 Antigen - metabolism
Adenocarcinoma - immunology
Adenocarcinoma - metabolism
Adenocarcinoma - secondary
Apoptosis
Case-Control Studies
CD133
Cell Proliferation
CSCs
Cytotoxicity
DKK3
Female
Gastric cancer
Humans
Immunological synapses
Immunology
Immunotherapy
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Killer Cells, Natural - pathology
Lymphatic Metastasis
Lymphocyte receptors
Male
Metabolic pathways
Middle Aged
Natural killer cells
Neoplasm Invasiveness
Neoplasm Staging
Neoplastic Stem Cells - immunology
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
NK Cell Lectin-Like Receptor Subfamily K - genetics
NK Cell Lectin-Like Receptor Subfamily K - metabolism
NK cells
NKG2 antigen
Prognosis
Stem cells
Stomach - immunology
Stomach - metabolism
Stomach - pathology
Stomach Neoplasms - immunology
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Survival Rate
Synapses
Tumor Cells, Cultured
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Summary:Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem‐like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D‐dependent manner. DKK3 has been demonstrated as a suppressor in many cancers. Interestingly, we found that DKK3 suppressed CD133‐induced activation in NK cells by inhibiting Erk pathway and immunological synapse (IS) formation. NK cells‐based CSCs immunotherapy may be a novel approach for cancer therapy.
ISSN:0899-1987
1098-2744
DOI:10.1002/mc.22628