miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells
Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvir...
Gespeichert in:
| Veröffentlicht in: | Cancers 2021-12, Vol.13 (24), p.6252 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 24 |
| container_start_page | 6252 |
| container_title | Cancers |
| container_volume | 13 |
| creator | Chang, Wei-An Tsai, Ming-Ju Hung, Jen-Yu Wu, Kuan-Li Tsai, Ying-Ming Huang, Yung-Chi Chang, Chao-Yuan Tsai, Pei-Hsun Hsu, Ya-Ling |
| description | Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer. |
| doi_str_mv | 10.3390/cancers13246252 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8699319</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2612737796</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-2d1d5cae3cb6303474cee583f8a35a58e416d7d31fd09ee42531f16430852a803</originalsourceid><addsrcrecordid>eNpdks1O3DAUha2qVUGUNbvKUjfdpPgvTrKpNIqgoE5phYBt5HFuZowSO7WdgXmuvmAdoIjijY_kz0fnXh2Ejij5wnlFjrWyGnygnAnJcvYG7TNSsEzKSrx9offQYQi3JB3OaSGL92iPi0qIsqD76M9gLjOakywfs9rZqIw1do1P7qNXGvp-6pXHNxCM7iHghQes8AXc4fNhmKzzsE5AdB5fbVTEp2qbZNwA_uXd2kMIxlnsOryckmf9EBcbi892o7s3Gv8w2juwW-OdHcDGgFc7vOgj-DnDg88GrIu7EWaXi--4TpHCB_SuU32Aw6f7AF2fnlzVZ9ny57fzerHMtGA0Zqylba4VcL2SnHBRCA2Ql7wrFc9VXoKgsi1aTruWVACC5UlSKTgpc6ZKwg_Q10ffcVoN0OqU0Ku-Gb0ZlN81Tpnm_xdrNs3abZtSVhWnVTL4_GTg3e8JQmwGE-atKgtuCg2TVDAuCRMJ_fQKvXWTt2m8mWIFL4pKJur4kUp7C8FD9xyGkmbuRPOqE-nHx5czPPP_GsD_AjpQteI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2612737796</pqid></control><display><type>article</type><title>miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells</title><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Chang, Wei-An ; Tsai, Ming-Ju ; Hung, Jen-Yu ; Wu, Kuan-Li ; Tsai, Ying-Ming ; Huang, Yung-Chi ; Chang, Chao-Yuan ; Tsai, Pei-Hsun ; Hsu, Ya-Ling</creator><creatorcontrib>Chang, Wei-An ; Tsai, Ming-Ju ; Hung, Jen-Yu ; Wu, Kuan-Li ; Tsai, Ying-Ming ; Huang, Yung-Chi ; Chang, Chao-Yuan ; Tsai, Pei-Hsun ; Hsu, Ya-Ling</creatorcontrib><description>Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13246252</identifier><identifier>PMID: 34944871</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiogenesis ; Animal models ; Antibodies ; Antigens ; Apoptosis ; Cancer therapies ; Cell growth ; Cytotoxicity ; Effector cells ; Extracellular vesicles ; Flow cytometry ; Hypoxia ; Inflammation ; Lung cancer ; Metastases ; MicroRNAs ; Natural killer cells ; Phenotypes ; Physiology ; Tumor microenvironment ; Tumorigenesis ; Tumors ; Vascular endothelial growth factor</subject><ispartof>Cancers, 2021-12, Vol.13 (24), p.6252</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-2d1d5cae3cb6303474cee583f8a35a58e416d7d31fd09ee42531f16430852a803</citedby><cites>FETCH-LOGICAL-c421t-2d1d5cae3cb6303474cee583f8a35a58e416d7d31fd09ee42531f16430852a803</cites><orcidid>0000-0002-0341-7747 ; 0000-0002-0049-5758 ; 0000-0003-3621-3334 ; 0000-0001-6662-6522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699319/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699319/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34944871$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Wei-An</creatorcontrib><creatorcontrib>Tsai, Ming-Ju</creatorcontrib><creatorcontrib>Hung, Jen-Yu</creatorcontrib><creatorcontrib>Wu, Kuan-Li</creatorcontrib><creatorcontrib>Tsai, Ying-Ming</creatorcontrib><creatorcontrib>Huang, Yung-Chi</creatorcontrib><creatorcontrib>Chang, Chao-Yuan</creatorcontrib><creatorcontrib>Tsai, Pei-Hsun</creatorcontrib><creatorcontrib>Hsu, Ya-Ling</creatorcontrib><title>miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.</description><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Cell growth</subject><subject>Cytotoxicity</subject><subject>Effector cells</subject><subject>Extracellular vesicles</subject><subject>Flow cytometry</subject><subject>Hypoxia</subject><subject>Inflammation</subject><subject>Lung cancer</subject><subject>Metastases</subject><subject>MicroRNAs</subject><subject>Natural killer cells</subject><subject>Phenotypes</subject><subject>Physiology</subject><subject>Tumor microenvironment</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdks1O3DAUha2qVUGUNbvKUjfdpPgvTrKpNIqgoE5phYBt5HFuZowSO7WdgXmuvmAdoIjijY_kz0fnXh2Ejij5wnlFjrWyGnygnAnJcvYG7TNSsEzKSrx9offQYQi3JB3OaSGL92iPi0qIsqD76M9gLjOakywfs9rZqIw1do1P7qNXGvp-6pXHNxCM7iHghQes8AXc4fNhmKzzsE5AdB5fbVTEp2qbZNwA_uXd2kMIxlnsOryckmf9EBcbi892o7s3Gv8w2juwW-OdHcDGgFc7vOgj-DnDg88GrIu7EWaXi--4TpHCB_SuU32Aw6f7AF2fnlzVZ9ny57fzerHMtGA0Zqylba4VcL2SnHBRCA2Ql7wrFc9VXoKgsi1aTruWVACC5UlSKTgpc6ZKwg_Q10ffcVoN0OqU0Ku-Gb0ZlN81Tpnm_xdrNs3abZtSVhWnVTL4_GTg3e8JQmwGE-atKgtuCg2TVDAuCRMJ_fQKvXWTt2m8mWIFL4pKJur4kUp7C8FD9xyGkmbuRPOqE-nHx5czPPP_GsD_AjpQteI</recordid><startdate>20211213</startdate><enddate>20211213</enddate><creator>Chang, Wei-An</creator><creator>Tsai, Ming-Ju</creator><creator>Hung, Jen-Yu</creator><creator>Wu, Kuan-Li</creator><creator>Tsai, Ying-Ming</creator><creator>Huang, Yung-Chi</creator><creator>Chang, Chao-Yuan</creator><creator>Tsai, Pei-Hsun</creator><creator>Hsu, Ya-Ling</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0341-7747</orcidid><orcidid>https://orcid.org/0000-0002-0049-5758</orcidid><orcidid>https://orcid.org/0000-0003-3621-3334</orcidid><orcidid>https://orcid.org/0000-0001-6662-6522</orcidid></search><sort><creationdate>20211213</creationdate><title>miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells</title><author>Chang, Wei-An ; Tsai, Ming-Ju ; Hung, Jen-Yu ; Wu, Kuan-Li ; Tsai, Ying-Ming ; Huang, Yung-Chi ; Chang, Chao-Yuan ; Tsai, Pei-Hsun ; Hsu, Ya-Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-2d1d5cae3cb6303474cee583f8a35a58e416d7d31fd09ee42531f16430852a803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Animal models</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Cell growth</topic><topic>Cytotoxicity</topic><topic>Effector cells</topic><topic>Extracellular vesicles</topic><topic>Flow cytometry</topic><topic>Hypoxia</topic><topic>Inflammation</topic><topic>Lung cancer</topic><topic>Metastases</topic><topic>MicroRNAs</topic><topic>Natural killer cells</topic><topic>Phenotypes</topic><topic>Physiology</topic><topic>Tumor microenvironment</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Wei-An</creatorcontrib><creatorcontrib>Tsai, Ming-Ju</creatorcontrib><creatorcontrib>Hung, Jen-Yu</creatorcontrib><creatorcontrib>Wu, Kuan-Li</creatorcontrib><creatorcontrib>Tsai, Ying-Ming</creatorcontrib><creatorcontrib>Huang, Yung-Chi</creatorcontrib><creatorcontrib>Chang, Chao-Yuan</creatorcontrib><creatorcontrib>Tsai, Pei-Hsun</creatorcontrib><creatorcontrib>Hsu, Ya-Ling</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Wei-An</au><au>Tsai, Ming-Ju</au><au>Hung, Jen-Yu</au><au>Wu, Kuan-Li</au><au>Tsai, Ying-Ming</au><au>Huang, Yung-Chi</au><au>Chang, Chao-Yuan</au><au>Tsai, Pei-Hsun</au><au>Hsu, Ya-Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-12-13</date><risdate>2021</risdate><volume>13</volume><issue>24</issue><spage>6252</spage><pages>6252-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>34944871</pmid><doi>10.3390/cancers13246252</doi><orcidid>https://orcid.org/0000-0002-0341-7747</orcidid><orcidid>https://orcid.org/0000-0002-0049-5758</orcidid><orcidid>https://orcid.org/0000-0003-3621-3334</orcidid><orcidid>https://orcid.org/0000-0001-6662-6522</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2021-12, Vol.13 (24), p.6252 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8699319 |
| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Angiogenesis Animal models Antibodies Antigens Apoptosis Cancer therapies Cell growth Cytotoxicity Effector cells Extracellular vesicles Flow cytometry Hypoxia Inflammation Lung cancer Metastases MicroRNAs Natural killer cells Phenotypes Physiology Tumor microenvironment Tumorigenesis Tumors Vascular endothelial growth factor |
| title | miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T08%3A44%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=miR-150-5p-Containing%20Extracellular%20Vesicles%20Are%20a%20New%20Immunoregulator%20That%20Favor%20the%20Progression%20of%20Lung%20Cancer%20in%20Hypoxic%20Microenvironments%20by%20Altering%20the%20Phenotype%20of%20NK%20Cells&rft.jtitle=Cancers&rft.au=Chang,%20Wei-An&rft.date=2021-12-13&rft.volume=13&rft.issue=24&rft.spage=6252&rft.pages=6252-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers13246252&rft_dat=%3Cproquest_pubme%3E2612737796%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2612737796&rft_id=info:pmid/34944871&rfr_iscdi=true |