Loading…

Attenuated anti-tumor activity of NK-92 cells by invasive human breast carcinoma MDA-MB-231 cells

Background Natural killer (NK) cells are typical innate lymphocytes that directly kill cancer cells. However, the anti-tumor function of NK cells can be modulated by various cancers in a tumor microenvironment. Objective We investigated whether the functional characteristics of NK cells are affected...

Full description

Saved in:
Bibliographic Details
Published in:Molecular & cellular toxicology 2020, 16(2), , pp.139-147
Main Authors: Lee, Hwan Hee, Cho, Hyosun
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503
cites cdi_FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503
container_end_page 147
container_issue 2
container_start_page 139
container_title Molecular & cellular toxicology
container_volume 16
creator Lee, Hwan Hee
Cho, Hyosun
description Background Natural killer (NK) cells are typical innate lymphocytes that directly kill cancer cells. However, the anti-tumor function of NK cells can be modulated by various cancers in a tumor microenvironment. Objective We investigated whether the functional characteristics of NK cells are affected by coculture with human breast carcinoma MCF-7 or MDA-MB231 cells and further examined the underlying molecular mechanisms that are associated with attenuated anti-tumor activity of NK cells. NK-92 cells were cocultured with MCF-7 or MDA-MB-231 cells at a ratio of 1:2 (target:effector) for 6 h. The cytotoxic effect of NK-92 cells was measured using CytoTox96 assay. The frequency of CD56, NKp30 + , NKp44 + , NKG2D + , and NKG2A + in NK-92 cells was investigated using individual fluorescent antibodies and flow cytometry. In addition, the production of cytokines was measured using Human Cytokine Array C1 kit. Proteins in cancer cell lysates were quantified and the expressions of PI3K, pAkt, Stat3, and pStat3 were examined by western blot analysis. Results The cytotoxicity of NK-92 cells is greater against MCF-7 than against MDA-MB-231 cells and cocultures with MCF-7 or MDA-MB-231 cells increased the frequency of CD56 dim population in NK-92 cells as well as IFN-γ production. The frequency of the NKp30 + or NKG2D + population in NK-92 cells was significantly decreased in coculture with MCF-7 or MDA-MB-231 cells. However, the frequency of NKG2A + expression in NK-92 cells was significantly increased in coculture with MCF-7 or MDA-MB-231 cells. The secretions of IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte–macrophage colony-stimulating factor were significantly higher in supernatant from coculture of NK-92 and MDA-MB-231 cells than in supernatants from NK-92 cell single culture or coculture of NK-92 and MCF-7 cells, which positively correlates with the enhanced expression of pStat3 in MDA-MB-231 cells cocultured with NK-92 cells. Conclusion These findings demonstrate that the anti-tumor function of NK-92 cells is significantly suppressed by an invasive human breast carcinoma, MDA-MB-231, and the impairment of NK-92 cell function is associated with the upregulation of the IL-6/Stat3 signaling pathway.
doi_str_mv 10.1007/s13273-019-00059-4
format article
fullrecord <record><control><sourceid>proquest_nrf_k</sourceid><recordid>TN_cdi_nrf_kci_oai_kci_go_kr_ARTI_9558609</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2394329693</sourcerecordid><originalsourceid>FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503</originalsourceid><addsrcrecordid>eNp9kDtPHDEURq0oSNlA_kAqS1QpDNe-Hj_KDa-gsCBFREpneRwPGHZnwPastP8-AxOJjuo253y6OoR85XDEAfRx4Sg0MuCWAUBjmfxAFgKsYEYq_ZEsuEbDlBR_PpHPpTwAKCmVXRC_rDX2o6_xL_V9TayOmyFTH2raprqjQ0evfzIraIjrdaHtjqZ-60vaRno_bnxP2xx9qTT4HFI_bDxdnS7Z6jsTyGfngOx1fl3il_93n_w-P7s9-cGubi4uT5ZXLGCDlcnWAOouirZtDQaN3oLUjTHQGRWVR6kBDEqJodOhsS2XHUbbemW95g3gPvk27_a5c48hucGn13s3uMfslr9uL51tGqPATuzhzD7l4XmMpbqHYcz99J4TaCUKqyxOlJipkIdScuzcU04bn3eOg3vJ7ubsbsruXrM7OUk4S2WC-7uY36bfsf4BfJOCdw</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2394329693</pqid></control><display><type>article</type><title>Attenuated anti-tumor activity of NK-92 cells by invasive human breast carcinoma MDA-MB-231 cells</title><source>Springer Nature</source><creator>Lee, Hwan Hee ; Cho, Hyosun</creator><creatorcontrib>Lee, Hwan Hee ; Cho, Hyosun</creatorcontrib><description>Background Natural killer (NK) cells are typical innate lymphocytes that directly kill cancer cells. However, the anti-tumor function of NK cells can be modulated by various cancers in a tumor microenvironment. Objective We investigated whether the functional characteristics of NK cells are affected by coculture with human breast carcinoma MCF-7 or MDA-MB231 cells and further examined the underlying molecular mechanisms that are associated with attenuated anti-tumor activity of NK cells. NK-92 cells were cocultured with MCF-7 or MDA-MB-231 cells at a ratio of 1:2 (target:effector) for 6 h. The cytotoxic effect of NK-92 cells was measured using CytoTox96 assay. The frequency of CD56, NKp30 + , NKp44 + , NKG2D + , and NKG2A + in NK-92 cells was investigated using individual fluorescent antibodies and flow cytometry. In addition, the production of cytokines was measured using Human Cytokine Array C1 kit. Proteins in cancer cell lysates were quantified and the expressions of PI3K, pAkt, Stat3, and pStat3 were examined by western blot analysis. Results The cytotoxicity of NK-92 cells is greater against MCF-7 than against MDA-MB-231 cells and cocultures with MCF-7 or MDA-MB-231 cells increased the frequency of CD56 dim population in NK-92 cells as well as IFN-γ production. The frequency of the NKp30 + or NKG2D + population in NK-92 cells was significantly decreased in coculture with MCF-7 or MDA-MB-231 cells. However, the frequency of NKG2A + expression in NK-92 cells was significantly increased in coculture with MCF-7 or MDA-MB-231 cells. The secretions of IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte–macrophage colony-stimulating factor were significantly higher in supernatant from coculture of NK-92 and MDA-MB-231 cells than in supernatants from NK-92 cell single culture or coculture of NK-92 and MCF-7 cells, which positively correlates with the enhanced expression of pStat3 in MDA-MB-231 cells cocultured with NK-92 cells. Conclusion These findings demonstrate that the anti-tumor function of NK-92 cells is significantly suppressed by an invasive human breast carcinoma, MDA-MB-231, and the impairment of NK-92 cell function is associated with the upregulation of the IL-6/Stat3 signaling pathway.</description><identifier>ISSN: 1738-642X</identifier><identifier>EISSN: 2092-8467</identifier><identifier>DOI: 10.1007/s13273-019-00059-4</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>1-Phosphatidylinositol 3-kinase ; Antitumor activity ; Antitumor agents ; Biomedical and Life Sciences ; Breast cancer ; Breast carcinoma ; CD56 antigen ; Cell Biology ; Cell culture ; Colony-stimulating factor ; Cytotoxicity ; Flow cytometry ; Granulocyte-macrophage colony-stimulating factor ; Interleukin 6 ; Interleukin 8 ; Invasiveness ; Life Sciences ; Lymphocytes ; Lysates ; Molecular modelling ; Monocyte chemoattractant protein ; Monocyte chemoattractant protein 1 ; Monocytes ; Natural killer cells ; NKG2 antigen ; Original Article ; Pharmacology/Toxicology ; Secretions ; Signal transduction ; Stat3 protein ; γ-Interferon ; 생물학</subject><ispartof>Molecular &amp; Cellular Toxicology, 2020, 16(2), , pp.139-147</ispartof><rights>The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Nature B.V. 2020</rights><rights>The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Nature B.V. 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503</citedby><cites>FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002618769$$DAccess content in National Research Foundation of Korea (NRF)$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hwan Hee</creatorcontrib><creatorcontrib>Cho, Hyosun</creatorcontrib><title>Attenuated anti-tumor activity of NK-92 cells by invasive human breast carcinoma MDA-MB-231 cells</title><title>Molecular &amp; cellular toxicology</title><addtitle>Mol. Cell. Toxicol</addtitle><description>Background Natural killer (NK) cells are typical innate lymphocytes that directly kill cancer cells. However, the anti-tumor function of NK cells can be modulated by various cancers in a tumor microenvironment. Objective We investigated whether the functional characteristics of NK cells are affected by coculture with human breast carcinoma MCF-7 or MDA-MB231 cells and further examined the underlying molecular mechanisms that are associated with attenuated anti-tumor activity of NK cells. NK-92 cells were cocultured with MCF-7 or MDA-MB-231 cells at a ratio of 1:2 (target:effector) for 6 h. The cytotoxic effect of NK-92 cells was measured using CytoTox96 assay. The frequency of CD56, NKp30 + , NKp44 + , NKG2D + , and NKG2A + in NK-92 cells was investigated using individual fluorescent antibodies and flow cytometry. In addition, the production of cytokines was measured using Human Cytokine Array C1 kit. Proteins in cancer cell lysates were quantified and the expressions of PI3K, pAkt, Stat3, and pStat3 were examined by western blot analysis. Results The cytotoxicity of NK-92 cells is greater against MCF-7 than against MDA-MB-231 cells and cocultures with MCF-7 or MDA-MB-231 cells increased the frequency of CD56 dim population in NK-92 cells as well as IFN-γ production. The frequency of the NKp30 + or NKG2D + population in NK-92 cells was significantly decreased in coculture with MCF-7 or MDA-MB-231 cells. However, the frequency of NKG2A + expression in NK-92 cells was significantly increased in coculture with MCF-7 or MDA-MB-231 cells. The secretions of IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte–macrophage colony-stimulating factor were significantly higher in supernatant from coculture of NK-92 and MDA-MB-231 cells than in supernatants from NK-92 cell single culture or coculture of NK-92 and MCF-7 cells, which positively correlates with the enhanced expression of pStat3 in MDA-MB-231 cells cocultured with NK-92 cells. Conclusion These findings demonstrate that the anti-tumor function of NK-92 cells is significantly suppressed by an invasive human breast carcinoma, MDA-MB-231, and the impairment of NK-92 cell function is associated with the upregulation of the IL-6/Stat3 signaling pathway.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Antitumor activity</subject><subject>Antitumor agents</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>CD56 antigen</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Colony-stimulating factor</subject><subject>Cytotoxicity</subject><subject>Flow cytometry</subject><subject>Granulocyte-macrophage colony-stimulating factor</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Invasiveness</subject><subject>Life Sciences</subject><subject>Lymphocytes</subject><subject>Lysates</subject><subject>Molecular modelling</subject><subject>Monocyte chemoattractant protein</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>Natural killer cells</subject><subject>NKG2 antigen</subject><subject>Original Article</subject><subject>Pharmacology/Toxicology</subject><subject>Secretions</subject><subject>Signal transduction</subject><subject>Stat3 protein</subject><subject>γ-Interferon</subject><subject>생물학</subject><issn>1738-642X</issn><issn>2092-8467</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kDtPHDEURq0oSNlA_kAqS1QpDNe-Hj_KDa-gsCBFREpneRwPGHZnwPastP8-AxOJjuo253y6OoR85XDEAfRx4Sg0MuCWAUBjmfxAFgKsYEYq_ZEsuEbDlBR_PpHPpTwAKCmVXRC_rDX2o6_xL_V9TayOmyFTH2raprqjQ0evfzIraIjrdaHtjqZ-60vaRno_bnxP2xx9qTT4HFI_bDxdnS7Z6jsTyGfngOx1fl3il_93n_w-P7s9-cGubi4uT5ZXLGCDlcnWAOouirZtDQaN3oLUjTHQGRWVR6kBDEqJodOhsS2XHUbbemW95g3gPvk27_a5c48hucGn13s3uMfslr9uL51tGqPATuzhzD7l4XmMpbqHYcz99J4TaCUKqyxOlJipkIdScuzcU04bn3eOg3vJ7ubsbsruXrM7OUk4S2WC-7uY36bfsf4BfJOCdw</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Lee, Hwan Hee</creator><creator>Cho, Hyosun</creator><general>Springer Singapore</general><general>Springer Nature B.V</general><general>대한독성 유전단백체 학회</general><scope>AAYXX</scope><scope>CITATION</scope><scope>ACYCR</scope></search><sort><creationdate>20200401</creationdate><title>Attenuated anti-tumor activity of NK-92 cells by invasive human breast carcinoma MDA-MB-231 cells</title><author>Lee, Hwan Hee ; Cho, Hyosun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Antitumor activity</topic><topic>Antitumor agents</topic><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast carcinoma</topic><topic>CD56 antigen</topic><topic>Cell Biology</topic><topic>Cell culture</topic><topic>Colony-stimulating factor</topic><topic>Cytotoxicity</topic><topic>Flow cytometry</topic><topic>Granulocyte-macrophage colony-stimulating factor</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Invasiveness</topic><topic>Life Sciences</topic><topic>Lymphocytes</topic><topic>Lysates</topic><topic>Molecular modelling</topic><topic>Monocyte chemoattractant protein</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Monocytes</topic><topic>Natural killer cells</topic><topic>NKG2 antigen</topic><topic>Original Article</topic><topic>Pharmacology/Toxicology</topic><topic>Secretions</topic><topic>Signal transduction</topic><topic>Stat3 protein</topic><topic>γ-Interferon</topic><topic>생물학</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hwan Hee</creatorcontrib><creatorcontrib>Cho, Hyosun</creatorcontrib><collection>CrossRef</collection><collection>Korean Citation Index (Open Access)</collection><jtitle>Molecular &amp; cellular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hwan Hee</au><au>Cho, Hyosun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Attenuated anti-tumor activity of NK-92 cells by invasive human breast carcinoma MDA-MB-231 cells</atitle><jtitle>Molecular &amp; cellular toxicology</jtitle><stitle>Mol. Cell. Toxicol</stitle><date>2020-04-01</date><risdate>2020</risdate><volume>16</volume><issue>2</issue><spage>139</spage><epage>147</epage><pages>139-147</pages><issn>1738-642X</issn><eissn>2092-8467</eissn><abstract>Background Natural killer (NK) cells are typical innate lymphocytes that directly kill cancer cells. However, the anti-tumor function of NK cells can be modulated by various cancers in a tumor microenvironment. Objective We investigated whether the functional characteristics of NK cells are affected by coculture with human breast carcinoma MCF-7 or MDA-MB231 cells and further examined the underlying molecular mechanisms that are associated with attenuated anti-tumor activity of NK cells. NK-92 cells were cocultured with MCF-7 or MDA-MB-231 cells at a ratio of 1:2 (target:effector) for 6 h. The cytotoxic effect of NK-92 cells was measured using CytoTox96 assay. The frequency of CD56, NKp30 + , NKp44 + , NKG2D + , and NKG2A + in NK-92 cells was investigated using individual fluorescent antibodies and flow cytometry. In addition, the production of cytokines was measured using Human Cytokine Array C1 kit. Proteins in cancer cell lysates were quantified and the expressions of PI3K, pAkt, Stat3, and pStat3 were examined by western blot analysis. Results The cytotoxicity of NK-92 cells is greater against MCF-7 than against MDA-MB-231 cells and cocultures with MCF-7 or MDA-MB-231 cells increased the frequency of CD56 dim population in NK-92 cells as well as IFN-γ production. The frequency of the NKp30 + or NKG2D + population in NK-92 cells was significantly decreased in coculture with MCF-7 or MDA-MB-231 cells. However, the frequency of NKG2A + expression in NK-92 cells was significantly increased in coculture with MCF-7 or MDA-MB-231 cells. The secretions of IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte–macrophage colony-stimulating factor were significantly higher in supernatant from coculture of NK-92 and MDA-MB-231 cells than in supernatants from NK-92 cell single culture or coculture of NK-92 and MCF-7 cells, which positively correlates with the enhanced expression of pStat3 in MDA-MB-231 cells cocultured with NK-92 cells. Conclusion These findings demonstrate that the anti-tumor function of NK-92 cells is significantly suppressed by an invasive human breast carcinoma, MDA-MB-231, and the impairment of NK-92 cell function is associated with the upregulation of the IL-6/Stat3 signaling pathway.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><doi>10.1007/s13273-019-00059-4</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 1738-642X
ispartof Molecular & Cellular Toxicology, 2020, 16(2), , pp.139-147
issn 1738-642X
2092-8467
language eng
recordid cdi_nrf_kci_oai_kci_go_kr_ARTI_9558609
source Springer Nature
subjects 1-Phosphatidylinositol 3-kinase
Antitumor activity
Antitumor agents
Biomedical and Life Sciences
Breast cancer
Breast carcinoma
CD56 antigen
Cell Biology
Cell culture
Colony-stimulating factor
Cytotoxicity
Flow cytometry
Granulocyte-macrophage colony-stimulating factor
Interleukin 6
Interleukin 8
Invasiveness
Life Sciences
Lymphocytes
Lysates
Molecular modelling
Monocyte chemoattractant protein
Monocyte chemoattractant protein 1
Monocytes
Natural killer cells
NKG2 antigen
Original Article
Pharmacology/Toxicology
Secretions
Signal transduction
Stat3 protein
γ-Interferon
생물학
title Attenuated anti-tumor activity of NK-92 cells by invasive human breast carcinoma MDA-MB-231 cells
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T08%3A09%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_nrf_k&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Attenuated%20anti-tumor%20activity%20of%20NK-92%20cells%20by%20invasive%20human%20breast%20carcinoma%20MDA-MB-231%20cells&rft.jtitle=Molecular%20&%20cellular%20toxicology&rft.au=Lee,%20Hwan%20Hee&rft.date=2020-04-01&rft.volume=16&rft.issue=2&rft.spage=139&rft.epage=147&rft.pages=139-147&rft.issn=1738-642X&rft.eissn=2092-8467&rft_id=info:doi/10.1007/s13273-019-00059-4&rft_dat=%3Cproquest_nrf_k%3E2394329693%3C/proquest_nrf_k%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c353t-4b8037fe2bbb83c73a90475880f86e6a3470083443cf7c59b14f3e9ba69a71503%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2394329693&rft_id=info:pmid/&rfr_iscdi=true