The Killer Cell Ig-like Receptor 2DL4 Expression in Human Mast Cells and Its Potential Role in Breast Cancer Invasion

Cancer Immunology Research
Chiyuki UeshimaHironori Haga

Abstract

The killer-cell Ig-like receptor (KIR) 2DL4 (CD158d) acts as a receptor for human leukocyte antigen (HLA)-G and is expressed on almost all human natural killer (NK) cells. The expression and function of KIR2DL4 in other hematopoietic cells is poorly understood. Here, we focused on human mast cells, which exhibit cytotoxic activity similar to that of NK cells. KIR2DL4 was detected in all examined human cultured mast cells established from peripheral blood derived from healthy volunteers (PB-mast), the human mast cell line LAD2, and human nonneoplastic mast cells, including those on pathologic specimens. An agonistic antibody against KIR2DL4 decreased KIT-mediated and IgE-triggered responses, and enhanced the granzyme B production by PB-mast and LAD2 cells, by activating Src homology 2-containing protein tyrosine phosphatase (SHP-2). Next, we performed a coculture assay between LAD2 cells and the HLA-G(+) cancer cells, MCF-7 and JEG-3, and showed that KIR2DL4 on LAD2 cells enhanced MMP-9 production and the invasive activity of both cell lines via HLA-G. Immunohistochemical analysis revealed that the direct interaction between HLA-G(+) breast cancer cells and KIR2DL4(+) tissue mast cells (observed in 12 of 36 cases; 33.3%) was sta...Continue Reading

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Citations

Feb 25, 2017·International Journal of Cancer. Journal International Du Cancer·Chandra KiranaEhud Hauben
Mar 3, 2018·Experimental Dermatology·Akihiko SugimotoHironori Haga
Nov 5, 2019·Current Pharmaceutical Design·George Anderson, Susana R Betancort Medina
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Nov 21, 2020·International Journal of Molecular Sciences·Jiji V D AttiaDaniëlle Krijgsman
Mar 27, 2018·The American Journal of Pathology·Chiyuki UeshimaHironori Haga

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