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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prostanoid induces premetastatic niche in regional lymph nodes</title><author><name sortKey="Ogawa, Fumihiro" sort="Ogawa, Fumihiro" uniqKey="Ogawa F" first="Fumihiro" last="Ogawa">Fumihiro Ogawa</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="JCI73530">Department of Clinical Research Center,</nlm:aff></affiliation></author><author><name sortKey="Amano, Hideki" sort="Amano, Hideki" uniqKey="Amano H" first="Hideki" last="Amano">Hideki Amano</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Eshima, Koji" sort="Eshima, Koji" uniqKey="Eshima K" first="Koji" last="Eshima">Koji Eshima</name><affiliation><nlm:aff wicri:cut=", and" id="JCI73530">Department of Immunology</nlm:aff></affiliation></author><author><name sortKey="Ito, Yoshiya" sort="Ito, Yoshiya" uniqKey="Ito Y" first="Yoshiya" last="Ito">Yoshiya Ito</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Matsui, Yoshio" sort="Matsui, Yoshio" uniqKey="Matsui Y" first="Yoshio" last="Matsui">Yoshio Matsui</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="JCI73530">Department of Thoracic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.</nlm:aff></affiliation></author><author><name sortKey="Hosono, Kanako" sort="Hosono, Kanako" uniqKey="Hosono K" first="Kanako" last="Hosono">Kanako Hosono</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Kitasato, Hidero" sort="Kitasato, Hidero" uniqKey="Kitasato H" first="Hidero" last="Kitasato">Hidero Kitasato</name><affiliation><nlm:aff id="JCI73530">Department of Microbiology, Kitasato University School of Allied Health Science, Kanagawa, Japan.</nlm:aff></affiliation></author><author><name sortKey="Iyoda, Akira" sort="Iyoda, Akira" uniqKey="Iyoda A" first="Akira" last="Iyoda">Akira Iyoda</name><affiliation><nlm:aff id="JCI73530">Department of Thoracic Surgery, Toho University School of Medicine, Tokyo, Japan.</nlm:aff></affiliation></author><author><name sortKey="Iwabuchi, Kazuya" sort="Iwabuchi, Kazuya" uniqKey="Iwabuchi K" first="Kazuya" last="Iwabuchi">Kazuya Iwabuchi</name><affiliation><nlm:aff wicri:cut=", and" id="JCI73530">Department of Immunology</nlm:aff></affiliation></author><author><name sortKey="Kumagai, Yuji" sort="Kumagai, Yuji" uniqKey="Kumagai Y" first="Yuji" last="Kumagai">Yuji Kumagai</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="JCI73530">Department of Clinical Research Center,</nlm:aff></affiliation></author><author><name sortKey="Satoh, Yukitoshi" sort="Satoh, Yukitoshi" uniqKey="Satoh Y" first="Yukitoshi" last="Satoh">Yukitoshi Satoh</name><affiliation><nlm:aff id="JCI73530">Department of Thoracic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.</nlm:aff></affiliation></author><author><name sortKey="Narumiya, Shuh" sort="Narumiya, Shuh" uniqKey="Narumiya S" first="Shuh" last="Narumiya">Shuh Narumiya</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.</nlm:aff></affiliation></author><author><name sortKey="Majima, Masataka" sort="Majima, Masataka" uniqKey="Majima M" first="Masataka" last="Majima">Masataka Majima</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25271626</idno><idno type="pmc">4347225</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347225</idno><idno type="RBID">PMC:4347225</idno><idno type="doi">10.1172/JCI73530</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002F27</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002F27</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prostanoid induces premetastatic niche in regional lymph nodes</title><author><name sortKey="Ogawa, Fumihiro" sort="Ogawa, Fumihiro" uniqKey="Ogawa F" first="Fumihiro" last="Ogawa">Fumihiro Ogawa</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="JCI73530">Department of Clinical Research Center,</nlm:aff></affiliation></author><author><name sortKey="Amano, Hideki" sort="Amano, Hideki" uniqKey="Amano H" first="Hideki" last="Amano">Hideki Amano</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Eshima, Koji" sort="Eshima, Koji" uniqKey="Eshima K" first="Koji" last="Eshima">Koji Eshima</name><affiliation><nlm:aff wicri:cut=", and" id="JCI73530">Department of Immunology</nlm:aff></affiliation></author><author><name sortKey="Ito, Yoshiya" sort="Ito, Yoshiya" uniqKey="Ito Y" first="Yoshiya" last="Ito">Yoshiya Ito</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Matsui, Yoshio" sort="Matsui, Yoshio" uniqKey="Matsui Y" first="Yoshio" last="Matsui">Yoshio Matsui</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="JCI73530">Department of Thoracic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.</nlm:aff></affiliation></author><author><name sortKey="Hosono, Kanako" sort="Hosono, Kanako" uniqKey="Hosono K" first="Kanako" last="Hosono">Kanako Hosono</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Kitasato, Hidero" sort="Kitasato, Hidero" uniqKey="Kitasato H" first="Hidero" last="Kitasato">Hidero Kitasato</name><affiliation><nlm:aff id="JCI73530">Department of Microbiology, Kitasato University School of Allied Health Science, Kanagawa, Japan.</nlm:aff></affiliation></author><author><name sortKey="Iyoda, Akira" sort="Iyoda, Akira" uniqKey="Iyoda A" first="Akira" last="Iyoda">Akira Iyoda</name><affiliation><nlm:aff id="JCI73530">Department of Thoracic Surgery, Toho University School of Medicine, Tokyo, Japan.</nlm:aff></affiliation></author><author><name sortKey="Iwabuchi, Kazuya" sort="Iwabuchi, Kazuya" uniqKey="Iwabuchi K" first="Kazuya" last="Iwabuchi">Kazuya Iwabuchi</name><affiliation><nlm:aff wicri:cut=", and" id="JCI73530">Department of Immunology</nlm:aff></affiliation></author><author><name sortKey="Kumagai, Yuji" sort="Kumagai, Yuji" uniqKey="Kumagai Y" first="Yuji" last="Kumagai">Yuji Kumagai</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="JCI73530">Department of Clinical Research Center,</nlm:aff></affiliation></author><author><name sortKey="Satoh, Yukitoshi" sort="Satoh, Yukitoshi" uniqKey="Satoh Y" first="Yukitoshi" last="Satoh">Yukitoshi Satoh</name><affiliation><nlm:aff id="JCI73530">Department of Thoracic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.</nlm:aff></affiliation></author><author><name sortKey="Narumiya, Shuh" sort="Narumiya, Shuh" uniqKey="Narumiya S" first="Shuh" last="Narumiya">Shuh Narumiya</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.</nlm:aff></affiliation></author><author><name sortKey="Majima, Masataka" sort="Majima, Masataka" uniqKey="Majima M" first="Masataka" last="Majima">Masataka Majima</name><affiliation><nlm:aff id="JCI73530">Department of Pharmacology,</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2–derived prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell–derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE<sub>2</sub> receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. Compared with WT CD11c<sup>+</sup> DCs, injection of EP3-deficient CD11c<sup>+</sup> DCs dramatically reduced accumulation of SDF-1<sup>+</sup>CD11c<sup>+</sup> DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, which may influence the fate of metastasized tumor cells, was also COX-2/EP3–dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3–dependent induction of SDF-1 and suggest that inhibition of this signaling axis may be an effective strategy to suppress premetastatic niche formation and LNM.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Invest</journal-id><journal-id journal-id-type="iso-abbrev">J. Clin. Invest</journal-id><journal-id journal-id-type="publisher-id">J CLIN INVEST</journal-id><journal-title-group><journal-title>The Journal of Clinical Investigation</journal-title></journal-title-group><issn pub-type="ppub">0021-9738</issn><issn pub-type="epub">1558-8238</issn><publisher><publisher-name>American Society for Clinical Investigation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25271626</article-id><article-id pub-id-type="pmc">4347225</article-id><article-id pub-id-type="publisher-id">73530</article-id><article-id pub-id-type="doi">10.1172/JCI73530</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Prostanoid induces premetastatic niche in regional lymph nodes</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ogawa</surname><given-names>Fumihiro</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref><xref ref-type="aff" rid="JCI73530">2</xref></contrib><contrib contrib-type="author"><name><surname>Amano</surname><given-names>Hideki</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref></contrib><contrib contrib-type="author"><name><surname>Eshima</surname><given-names>Koji</given-names></name><xref ref-type="aff" rid="JCI73530">3</xref></contrib><contrib contrib-type="author"><name><surname>Ito</surname><given-names>Yoshiya</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref></contrib><contrib contrib-type="author"><name><surname>Matsui</surname><given-names>Yoshio</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref><xref ref-type="aff" rid="JCI73530">4</xref></contrib><contrib contrib-type="author"><name><surname>Hosono</surname><given-names>Kanako</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref></contrib><contrib contrib-type="author"><name><surname>Kitasato</surname><given-names>Hidero</given-names></name><xref ref-type="aff" rid="JCI73530">5</xref></contrib><contrib contrib-type="author"><name><surname>Iyoda</surname><given-names>Akira</given-names></name><xref ref-type="aff" rid="JCI73530">6</xref></contrib><contrib contrib-type="author"><name><surname>Iwabuchi</surname><given-names>Kazuya</given-names></name><xref ref-type="aff" rid="JCI73530">3</xref></contrib><contrib contrib-type="author"><name><surname>Kumagai</surname><given-names>Yuji</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref><xref ref-type="aff" rid="JCI73530">2</xref></contrib><contrib contrib-type="author"><name><surname>Satoh</surname><given-names>Yukitoshi</given-names></name><xref ref-type="aff" rid="JCI73530">4</xref></contrib><contrib contrib-type="author"><name><surname>Narumiya</surname><given-names>Shuh</given-names></name><xref ref-type="aff" rid="JCI73530">7</xref></contrib><contrib contrib-type="author"><name><surname>Majima</surname><given-names>Masataka</given-names></name><xref ref-type="aff" rid="JCI73530">1</xref></contrib></contrib-group><aff id="JCI73530"><label>1</label>Department of Pharmacology,<label>2</label>Department of Clinical Research Center,<label>3</label>Department of Immunology, and<label>4</label>Department of Thoracic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.<label>5</label>Department of Microbiology, Kitasato University School of Allied Health Science, Kanagawa, Japan.<label>6</label>Department of Thoracic Surgery, Toho University School of Medicine, Tokyo, Japan.<label>7</label>Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.</aff><author-notes><corresp>Address correspondence to: Masataka Majima, Department of Pharmacology, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. Phone: 81427788822; E-mail: <email>mmajima@med.kitasato-u.ac.jp</email>.</corresp><fn><p><bold>Authorship note:</bold> Fumihiro Ogawa, Hideki Amano, and Koji Eshima contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>1</day><month>10</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>3</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>3</day><month>2</month><year>2015</year></pub-date><pmc-comment> PMC Release delay is 3 months and 0 days and was based on the
<volume>124</volume><issue>11</issue><fpage>4882</fpage><lpage>4894</lpage><history><date date-type="received"><day>1</day><month>10</month><year>2013</year></date><date date-type="accepted"><day>21</day><month>8</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014, American Society for Clinical Investigation</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>American Society for Clinical Investigation</copyright-holder></permissions><abstract><p>The lymphatic system is an important route for cancer dissemination, and lymph node metastasis (LNM) serves as a critical prognostic determinant in cancer patients. We investigated the contribution of COX-2–derived prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) in the formation of a premetastatic niche and LNM. A murine model of Lewis lung carcinoma (LLC) cell metastasis revealed that COX-2 is expressed in DCs from the early stage in the lymph node subcapsular regions, and COX-2 inhibition markedly suppressed mediastinal LNM. Stromal cell–derived factor-1 (SDF-1) was elevated in DCs before LLC cell infiltration to the lymph nodes, and a COX-2 inhibitor, an SDF-1 antagonist, and a CXCR4 neutralizing antibody all reduced LNM. Moreover, LNM was reduced in mice lacking the PGE<sub>2</sub> receptor EP3, and stimulation of cultured DCs with an EP3 agonist increased SDF-1 production. Compared with WT CD11c<sup>+</sup> DCs, injection of EP3-deficient CD11c<sup>+</sup> DCs dramatically reduced accumulation of SDF-1<sup>+</sup>CD11c<sup>+</sup> DCs in regional LNs and LNM in LLC-injected mice. Accumulation of Tregs and lymph node lymphangiogenesis, which may influence the fate of metastasized tumor cells, was also COX-2/EP3–dependent. These results indicate that DCs induce a premetastatic niche during LNM via COX-2/EP3–dependent induction of SDF-1 and suggest that inhibition of this signaling axis may be an effective strategy to suppress premetastatic niche formation and LNM.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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