PMID- 25735953 OWN - NLM STAT- MEDLINE DCOM- 20160505 LR - 20220317 IS - 2326-6074 (Electronic) IS - 2326-6066 (Linking) VI - 3 IP - 8 DP - 2015 Aug TI - The Killer Cell Ig-like Receptor 2DL4 Expression in Human Mast Cells and Its Potential Role in Breast Cancer Invasion. PG - 871-80 LID - 10.1158/2326-6066.CIR-14-0199 [doi] AB - 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 statistically correlated with the presence of lymph node metastasis or lymph-vascular invasion (observed in 11 of 12 cases; 91.7%; chi(2) = 7.439; P < 0.01; degrees of freedom, 1) in the clinical samples. These findings suggest that the KIR2DL4 on human mast cells facilitates HLA-G-expressing cancer invasion and the subsequent metastasis. CI - (c)2015 American Association for Cancer Research. FAU - Ueshima, Chiyuki AU - Ueshima C AD - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Kataoka, Tatsuki R AU - Kataoka TR AD - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. trkataoka@yahoo.co.jp. FAU - Hirata, Masahiro AU - Hirata M AD - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. FAU - Furuhata, Ayako AU - Furuhata A AD - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. FAU - Suzuki, Eiji AU - Suzuki E AD - Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan. FAU - Toi, Masakazu AU - Toi M AD - Department of Breast Surgery, Kyoto University Hospital, Kyoto, Japan. FAU - Tsuruyama, Tatsuaki AU - Tsuruyama T AD - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. FAU - Okayama, Yoshimichi AU - Okayama Y AD - Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, Japan. FAU - Haga, Hironori AU - Haga H AD - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150303 PL - United States TA - Cancer Immunol Res JT - Cancer immunology research JID - 101614637 RN - 0 (Antibodies, Monoclonal) RN - 0 (Biomarkers, Tumor) RN - 0 (HLA-G Antigens) RN - 0 (Receptors, KIR2DL4) RN - 37341-29-0 (Immunoglobulin E) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) RN - EC 3.1.3.48 (PTPN11 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) SB - IM MH - Aged MH - Antibodies, Monoclonal/pharmacology MH - Biomarkers, Tumor MH - Breast Neoplasms/*genetics/*immunology/pathology/therapy MH - Cell Line, Tumor MH - Female MH - *Gene Expression MH - HLA-G Antigens/immunology/metabolism MH - Humans MH - Immunoglobulin E/immunology MH - Mast Cells/*immunology/*metabolism MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Protein Binding MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism MH - Proto-Oncogene Proteins c-kit/metabolism MH - Receptors, KIR2DL4/antagonists & inhibitors/*genetics/metabolism EDAT- 2015/03/05 06:00 MHDA- 2016/05/06 06:00 CRDT- 2015/03/05 06:00 PHST- 2014/10/22 00:00 [received] PHST- 2015/02/24 00:00 [accepted] PHST- 2015/03/05 06:00 [entrez] PHST- 2015/03/05 06:00 [pubmed] PHST- 2016/05/06 06:00 [medline] AID - 2326-6066.CIR-14-0199 [pii] AID - 10.1158/2326-6066.CIR-14-0199 [doi] PST - ppublish SO - Cancer Immunol Res. 2015 Aug;3(8):871-80. doi: 10.1158/2326-6066.CIR-14-0199. Epub 2015 Mar 3.