Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets.
Identifieur interne : 001773 ( Main/Exploration ); précédent : 001772; suivant : 001774Interleukin-6-dependent growth in a newly established plasmablastic lymphoma cell line and its therapeutic targets.
Auteurs : Sohtaro Mine [Japon] ; Tsunekazu Hishima [Japon] ; Akihiko Suganuma [Japon] ; Hitomi Fukumoto [Japon] ; Yuko Sato [Japon] ; Michiyo Kataoka [Japon] ; Tsuyoshi Sekizuka [Japon] ; Makoto Kuroda [Japon] ; Tadaki Suzuki [Japon] ; Hideki Hasegawa [Japon] ; Masashi Fukayama [Japon] ; Harutaka Katano [Japon]Source :
- Scientific reports [ 2045-2322 ] ; 2017.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Anticorps monoclonaux humanisés, Humains, Immunophénotypage, Interleukine-6 (pharmacologie), Lignée cellulaire tumorale, Lymphome plasmoblastique (anatomopathologie), Lymphome plasmoblastique (immunologie), Lymphome plasmoblastique (étiologie), Milieux de culture (), Mâle, Syndrome d'immunodéficience acquise (), Techniques de culture cellulaire ().
- MESH :
- anatomopathologie : Lymphome plasmoblastique.
- immunologie : Lymphome plasmoblastique.
- pharmacologie : Interleukine-6.
- étiologie : Lymphome plasmoblastique.
- Adulte d'âge moyen, Anticorps monoclonaux humanisés, Humains, Immunophénotypage, Lignée cellulaire tumorale, Milieux de culture, Mâle, Syndrome d'immunodéficience acquise, Techniques de culture cellulaire.
English descriptors
- KwdEn :
- Acquired Immunodeficiency Syndrome (complications), Antibodies, Monoclonal, Humanized, Cell Culture Techniques (methods), Cell Line, Tumor, Culture Media (chemistry), Humans, Immunophenotyping, Interleukin-6 (pharmacology), Male, Middle Aged, Plasmablastic Lymphoma (etiology), Plasmablastic Lymphoma (immunology), Plasmablastic Lymphoma (pathology).
- MESH :
- chemical , chemistry : Culture Media.
- chemical , pharmacology : Interleukin-6.
- chemical : Antibodies, Monoclonal, Humanized.
- complications : Acquired Immunodeficiency Syndrome.
- etiology : Plasmablastic Lymphoma.
- immunology : Plasmablastic Lymphoma.
- methods : Cell Culture Techniques.
- pathology : Plasmablastic Lymphoma.
- Cell Line, Tumor, Humans, Immunophenotyping, Male, Middle Aged.
Abstract
Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(-) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.
DOI: 10.1038/s41598-017-10684-5
PubMed: 28860565
Affiliations:
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Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hasegawa, Hideki" sort="Hasegawa, Hideki" uniqKey="Hasegawa H" first="Hideki" last="Hasegawa">Hideki Hasegawa</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fukayama, Masashi" sort="Fukayama, Masashi" uniqKey="Fukayama M" first="Masashi" last="Fukayama">Masashi 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Hishima</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, Tokyo Metropolitan Komagome Hospital, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Suganuma, Akihiko" sort="Suganuma, Akihiko" uniqKey="Suganuma A" first="Akihiko" last="Suganuma">Akihiko Suganuma</name><affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Infectious Diseases, Tokyo Metropolitan Komagome Hospital, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fukumoto, Hitomi" sort="Fukumoto, Hitomi" uniqKey="Fukumoto H" first="Hitomi" last="Fukumoto">Hitomi Fukumoto</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Sato, Yuko" sort="Sato, Yuko" uniqKey="Sato Y" first="Yuko" last="Sato">Yuko Sato</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kataoka, Michiyo" sort="Kataoka, Michiyo" uniqKey="Kataoka M" first="Michiyo" last="Kataoka">Michiyo Kataoka</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Sekizuka, Tsuyoshi" sort="Sekizuka, Tsuyoshi" uniqKey="Sekizuka T" first="Tsuyoshi" last="Sekizuka">Tsuyoshi Sekizuka</name><affiliation wicri:level="3"><nlm:affiliation>Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Kuroda, Makoto" sort="Kuroda, Makoto" uniqKey="Kuroda M" first="Makoto" last="Kuroda">Makoto Kuroda</name><affiliation wicri:level="3"><nlm:affiliation>Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Pathogen Genomic Center, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Hasegawa, Hideki" sort="Hasegawa, Hideki" uniqKey="Hasegawa H" first="Hideki" last="Hasegawa">Hideki Hasegawa</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Fukayama, Masashi" sort="Fukayama, Masashi" uniqKey="Fukayama M" first="Masashi" last="Fukayama">Masashi Fukayama</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Katano, Harutaka" sort="Katano, Harutaka" uniqKey="Katano H" first="Harutaka" last="Katano">Harutaka Katano</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan. katano@nih.go.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology, National Institute of Infectious Diseases, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acquired Immunodeficiency Syndrome (complications)</term><term>Antibodies, Monoclonal, Humanized</term><term>Cell Culture Techniques (methods)</term><term>Cell Line, Tumor</term><term>Culture Media (chemistry)</term><term>Humans</term><term>Immunophenotyping</term><term>Interleukin-6 (pharmacology)</term><term>Male</term><term>Middle Aged</term><term>Plasmablastic Lymphoma (etiology)</term><term>Plasmablastic Lymphoma (immunology)</term><term>Plasmablastic Lymphoma (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Anticorps monoclonaux humanisés</term><term>Humains</term><term>Immunophénotypage</term><term>Interleukine-6 (pharmacologie)</term><term>Lignée cellulaire tumorale</term><term>Lymphome plasmoblastique (anatomopathologie)</term><term>Lymphome plasmoblastique (immunologie)</term><term>Lymphome plasmoblastique (étiologie)</term><term>Milieux de culture ()</term><term>Mâle</term><term>Syndrome d'immunodéficience acquise ()</term><term>Techniques de culture cellulaire ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Culture Media</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphome plasmoblastique</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Acquired Immunodeficiency Syndrome</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Plasmablastic Lymphoma</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lymphome plasmoblastique</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Plasmablastic Lymphoma</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Cell Culture Techniques</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Plasmablastic Lymphoma</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Lymphome plasmoblastique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Humans</term><term>Immunophenotyping</term><term>Male</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Anticorps monoclonaux humanisés</term><term>Humains</term><term>Immunophénotypage</term><term>Lignée cellulaire tumorale</term><term>Milieux de culture</term><term>Mâle</term><term>Syndrome d'immunodéficience acquise</term><term>Techniques de culture cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Plasmablastic lymphoma (PBL) is a rare, highly aggressive subtype of non-Hodgkin lymphoma with plasma-cell differentiation occurring typically in immune-suppressed patients such as those with AIDS. This study reports the establishment and characterization of a new cell line, PBL-1, derived from a patient with AIDS-associated PBL. Morphological assessment of PBL-1 indicated plasma-cell differentiation with a CD20(-) CD38(+) CD138(+) immunophenotype and IgH/c-myc translocation. The cell line harbours Epstein-Barr virus, but a 52.7-kbp length defect was identified in its genome, resulting in no expression of viral microRNAs encoded in the BamHI-A Rightward Transcript region. Importantly, supplementation of culture medium with >5 ng/mL of interleukin-6 (IL-6) was required for PBL-1 growth. Starvation of IL-6 or addition of tocilizumab, an inhibitory antibody for the IL-6 receptor, induced apoptosis of PBL-1. Transduction of IL-6 into PBL-1 by lentivirus vector induced autologous growth without IL-6 supplementation of culture medium. These data indicate the IL-6 dependency of PBL-1 for proliferation and survival. mTOR inhibitors induced cell death effectively, suggesting mTOR in the IL-6 signalling pathway is a potential therapeutic target for PBL. This established PBL cell line will be a useful tool to further understand the pathophysiology of PBL and aid the future development of PBL treatment.</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li></orgName></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Mine, Sohtaro" sort="Mine, Sohtaro" uniqKey="Mine S" first="Sohtaro" last="Mine">Sohtaro Mine</name></region><name sortKey="Fukayama, Masashi" sort="Fukayama, Masashi" uniqKey="Fukayama M" first="Masashi" last="Fukayama">Masashi Fukayama</name><name sortKey="Fukumoto, Hitomi" sort="Fukumoto, Hitomi" uniqKey="Fukumoto H" first="Hitomi" last="Fukumoto">Hitomi Fukumoto</name><name sortKey="Hasegawa, Hideki" sort="Hasegawa, Hideki" uniqKey="Hasegawa H" first="Hideki" last="Hasegawa">Hideki Hasegawa</name><name sortKey="Hishima, Tsunekazu" sort="Hishima, Tsunekazu" uniqKey="Hishima T" first="Tsunekazu" last="Hishima">Tsunekazu Hishima</name><name sortKey="Katano, Harutaka" sort="Katano, Harutaka" uniqKey="Katano H" first="Harutaka" last="Katano">Harutaka Katano</name><name sortKey="Kataoka, Michiyo" sort="Kataoka, Michiyo" uniqKey="Kataoka M" first="Michiyo" last="Kataoka">Michiyo Kataoka</name><name sortKey="Kuroda, Makoto" sort="Kuroda, Makoto" uniqKey="Kuroda M" first="Makoto" last="Kuroda">Makoto Kuroda</name><name sortKey="Sato, Yuko" sort="Sato, Yuko" uniqKey="Sato Y" first="Yuko" last="Sato">Yuko Sato</name><name sortKey="Sekizuka, Tsuyoshi" sort="Sekizuka, Tsuyoshi" uniqKey="Sekizuka T" first="Tsuyoshi" last="Sekizuka">Tsuyoshi Sekizuka</name><name sortKey="Suganuma, Akihiko" sort="Suganuma, Akihiko" uniqKey="Suganuma A" first="Akihiko" last="Suganuma">Akihiko Suganuma</name><name sortKey="Suzuki, Tadaki" sort="Suzuki, Tadaki" uniqKey="Suzuki T" first="Tadaki" last="Suzuki">Tadaki Suzuki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:28860565" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a TocilizumabV1
| This area was generated with Dilib version V0.6.34. |  |