The bidirectional crosstalk between metastatic uveal melanoma cells and hepatic stellate cells engenders an inflammatory microenvironment
Identifieur interne : 000009 ( Hal/Checkpoint ); précédent : 000008; suivant : 000010The bidirectional crosstalk between metastatic uveal melanoma cells and hepatic stellate cells engenders an inflammatory microenvironment
Auteurs : Narjes Babchia [France] ; Solange Landreville [Canada] ; Bruno Clement [France] ; Cédric Coulouarn [France] ; Frederic Mouriaux [France]Source :
- Experimental Eye Research [ 0014-4835 ] ; 2019.
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Abstract
Uveal melanoma is the most common primary ocular neoplasm in adults. It is peculiar for its hematogenous dissemination and its high propensity to spread to the liver. Current treatments rarely prolong patient survival. We hypothesized that metastatic uveal melanoma cells modulate the function of surrounding hepatic stellate cells to facilitate their own growth and survival. This study was conducted to investigate the role of the hepatic microenvironment on uveal melanoma aggressiveness. We demonstrated that the paracrine signaling of surrounding hepatic stellate cells have more transcriptional impact on metastatic uveal melanoma cells. Upregulated transcripts were linked to inflammation and included several interleukins. The uveal melanoma-stellate cell crosstalk induced as well the expression of transmembrane integrins. In addition, the interleukin-6 receptor inhibitor Tocilizumab did not reduce the growth of uveal melanoma cells. Our results provide evidence that inflammatory mediators are key players in the homing of uveal melanoma cells to the liver. The bidirectional crosstalk between uveal melanoma cells and hepatic stellate cells involved pro-fibrogenic interleukins. The inflammatory characteristics of the metastatic microenvironment might offer relevant therapeutic opportunities in uveal melanoma.
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DOI: 10.1016/j.exer.2019.02.012
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CHU Rennes (Bât 15) - Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France</addrLine> <country key="FR"></country> </address> <ref type="url">https://numecan.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-105160" type="direct"></relation> <relation active="#struct-528860" type="indirect"></relation> <relation name="U1241" active="#struct-303623" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-105160" type="direct"><org type="institution" xml:id="struct-105160" status="VALID"> <orgName>Université de Rennes 1</orgName> <orgName type="acronym">UR1</orgName> <desc> <address> <addrLine>2 rue du Thabor - CS 46510 - 35065 Rennes cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-528860" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-528860" type="indirect"><org type="regroupinstitution" xml:id="struct-528860" status="VALID"> <orgName>Université de Rennes</orgName> <orgName type="acronym">UNIV-RENNES</orgName> <date type="start">2018-01-01</date> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle name="U1241" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Rennes</settlement><region type="region" nuts="2">Région Bretagne</region></placeName><orgName type="university">Université de Rennes 1</orgName><orgName type="institution" wicri:auto="newGroup">Université européenne de Bretagne</orgName></affiliation></author><author><name sortKey="Landreville, Solange" sort="Landreville, Solange" uniqKey="Landreville S" first="Solange" last="Landreville">Solange Landreville</name><affiliation wicri:level="1"><hal:affiliation type="regroupinstitution" xml:id="struct-540997" status="VALID"> <orgName>CHU de Québec–Université Laval</orgName> <desc> <address> <addrLine>Québec</addrLine> <country key="CA"></country> </address> </desc> </hal:affiliation><country>Canada</country></affiliation></author><author><name sortKey="Clement, Bruno" sort="Clement, Bruno" uniqKey="Clement B" first="Bruno" last="Clement">Bruno Clement</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-480788" status="VALID"> <orgName>Nutrition, Métabolismes et Cancer</orgName> <orgName type="acronym">NuMeCan</orgName> <date type="start">2017-01-01</date> <desc> <address> <addrLine>Campus Villejean (Bât 8) - 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CHU Rennes (Bât 15) - Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France</addrLine> <country key="FR"></country> </address> <ref type="url">https://numecan.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-105160" type="direct"></relation> <relation active="#struct-528860" type="indirect"></relation> <relation name="U1241" active="#struct-303623" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-105160" type="direct"><org type="institution" xml:id="struct-105160" status="VALID"> <orgName>Université de Rennes 1</orgName> <orgName type="acronym">UR1</orgName> <desc> <address> <addrLine>2 rue du Thabor - CS 46510 - 35065 Rennes cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-528860" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-528860" type="indirect"><org type="regroupinstitution" xml:id="struct-528860" status="VALID"> <orgName>Université de Rennes</orgName> <orgName type="acronym">UNIV-RENNES</orgName> <date type="start">2018-01-01</date> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle name="U1241" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Rennes</settlement><region type="region" nuts="2">Région Bretagne</region></placeName><orgName type="university">Université de Rennes 1</orgName><orgName type="institution" wicri:auto="newGroup">Université européenne de Bretagne</orgName></affiliation></author></analytic><idno type="DOI">10.1016/j.exer.2019.02.012</idno><series><title level="j">Experimental Eye Research</title><idno type="ISSN">0014-4835</idno><imprint><date type="datePub">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Inflammation</term><term>Metastases</term><term>Microenvironment</term><term>Tocilizumab</term><term>Uveal melanoma</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>Uveal melanoma is the most common primary ocular neoplasm in adults. It is peculiar for its hematogenous dissemination and its high propensity to spread to the liver. Current treatments rarely prolong patient survival. We hypothesized that metastatic uveal melanoma cells modulate the function of surrounding hepatic stellate cells to facilitate their own growth and survival. This study was conducted to investigate the role of the hepatic microenvironment on uveal melanoma aggressiveness. We demonstrated that the paracrine signaling of surrounding hepatic stellate cells have more transcriptional impact on metastatic uveal melanoma cells. Upregulated transcripts were linked to inflammation and included several interleukins. The uveal melanoma-stellate cell crosstalk induced as well the expression of transmembrane integrins. In addition, the interleukin-6 receptor inhibitor Tocilizumab did not reduce the growth of uveal melanoma cells. Our results provide evidence that inflammatory mediators are key players in the homing of uveal melanoma cells to the liver. The bidirectional crosstalk between uveal melanoma cells and hepatic stellate cells involved pro-fibrogenic interleukins. The inflammatory characteristics of the metastatic microenvironment might offer relevant therapeutic opportunities in uveal melanoma.</p> </div></front></TEI><hal api="V3"> <titleStmt> <title xml:lang="en">The bidirectional crosstalk between metastatic uveal melanoma cells and hepatic stellate cells engenders an inflammatory microenvironment</title> <author role="aut"> <persName> <forename type="first">Narjes</forename> <surname>Babchia</surname> </persName> <idno type="halauthorid">11420110</idno> <affiliation ref="#struct-480788"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Solange</forename> <surname>Landreville</surname> </persName> <idno type="halauthorid">1503407</idno> <affiliation ref="#struct-540997"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Bruno</forename> <surname>Clement</surname> </persName> <idno type="halauthorid">957374</idno> <affiliation ref="#struct-480788"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Cédric</forename> <surname>Coulouarn</surname> </persName> <idno type="halauthorid">892711</idno> <affiliation ref="#struct-480788"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Frederic</forename> <surname>Mouriaux</surname> </persName> <idno type="halauthorid">11300372</idno> <affiliation ref="#struct-480788"></affiliation> </author> <editor role="depositor"> <persName> <forename>Laurent</forename> <surname>Jonchère</surname> </persName> <email type="md5">8503b29898396526c56d96d8ae07e3e5</email> <email type="domain">univ-rennes1.fr</email> </editor> <funder>N.B. was supported by a PRESTIGE grant award co-funded by the European Union, and a SAD Fellowship from the Conseil Régional Bretagne. S.L. is a Research Scholar of the Fonds de Recherche du Québec - Santé (FRQS). This study was supported by Inserm, Université de Rennes 1, Association de la lutte contre le cancer, Comité départemental d’Ille-et-Vilaine de la Ligue contre le cancer, and International Networking Funding Program of the FRQS Vision Health Research Network.</funder> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2019-04-16 13:51:25</date> <date type="whenModified">2019-04-16 16:20:50</date> <date type="whenReleased">2019-04-16 16:20:50</date> <date type="whenProduced">2019</date> <date type="whenEndEmbargoed">2019-08-13</date> <ref type="file" target="https://hal-univ-rennes1.archives-ouvertes.fr/hal-02050392/document"> <date notBefore="2019-08-13"></date> </ref> <ref type="file" subtype="author" n="1" target="https://hal-univ-rennes1.archives-ouvertes.fr/hal-02050392/file/Babchia_et_al-2019-The_bidirectional_crosstalk_between_metastatic_uveal_melanoma_cells_and_hepatic.pdf"> <date notBefore="2019-08-13"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="113861"> <persName> <forename>Laurent</forename> <surname>Jonchère</surname> </persName> <email type="md5">8503b29898396526c56d96d8ae07e3e5</email> <email type="domain">univ-rennes1.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">hal-02050392</idno> <idno type="halUri">https://hal-univ-rennes1.archives-ouvertes.fr/hal-02050392</idno> <idno type="halBibtex">babchia:hal-02050392</idno> <idno type="halRefHtml">Experimental Eye Research, Elsevier, 2019, 181, pp.213-222. ⟨10.1016/j.exer.2019.02.012⟩</idno> <idno type="halRef">Experimental Eye Research, Elsevier, 2019, 181, pp.213-222. ⟨10.1016/j.exer.2019.02.012⟩</idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="UNIV-RENNES1">Université de Rennes 1</idno> <idno type="stamp" n="STATS-UR1">Statistiques-HAL-UR1</idno> <idno type="stamp" n="NUMECAN">Nutrition, Métabolismes et Cancer</idno> <idno type="stamp" n="NUMECAN-TGTC" corresp="NUMECAN">TGTC</idno> <idno type="stamp" n="UR1-UFR-SVE">UFR SVE Sciences de la vie et de l'environnement</idno> <idno type="stamp" n="UR1-HAL">Publications labos UR1 dans HAL-Rennes 1</idno> <idno type="stamp" n="UR1-SDV">UR1 - publications SDV</idno> <idno type="stamp" n="TEST-UR-CSS">TEST Université de Rennes CSS</idno> <idno type="stamp" n="UNIV-RENNES">Université de Rennes</idno> </seriesStmt> <notesStmt> <note type="audience" n="2">International</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <sourceDesc> <biblStruct> <analytic> <title xml:lang="en">The bidirectional crosstalk between metastatic uveal melanoma cells and hepatic stellate cells engenders an inflammatory microenvironment</title> <author role="aut"> <persName> <forename type="first">Narjes</forename> <surname>Babchia</surname> </persName> <idno type="halauthorid">11420110</idno> <affiliation ref="#struct-480788"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Solange</forename> <surname>Landreville</surname> </persName> <idno type="halauthorid">1503407</idno> <affiliation ref="#struct-540997"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Bruno</forename> <surname>Clement</surname> </persName> <idno type="halauthorid">957374</idno> <affiliation ref="#struct-480788"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Cédric</forename> <surname>Coulouarn</surname> </persName> <idno type="halauthorid">892711</idno> <affiliation ref="#struct-480788"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Frederic</forename> <surname>Mouriaux</surname> </persName> <idno type="halauthorid">11300372</idno> <affiliation ref="#struct-480788"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">13195</idno> <idno type="issn">0014-4835</idno> <idno type="eissn">1096-0007</idno> <title level="j">Experimental Eye Research</title> <imprint> <publisher>Elsevier</publisher> <biblScope unit="volume">181</biblScope> <biblScope unit="pp">213-222</biblScope> <date type="datePub">2019</date> <date type="dateEpub">2019-02-13</date> </imprint> </monogr> <idno type="doi">10.1016/j.exer.2019.02.012</idno> <idno type="pubmed">30771295</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">Inflammation</term> <term xml:lang="en">Metastases</term> <term xml:lang="en">Tocilizumab</term> <term xml:lang="en">Uveal melanoma</term> <term xml:lang="en">Microenvironment</term> </keywords> <classCode scheme="halDomain" n="sdv.can">Life Sciences [q-bio]/Cancer</classCode> <classCode scheme="halDomain" n="sdv.mhep.os">Life Sciences [q-bio]/Human health and pathology/Sensory Organs</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <abstract xml:lang="en"> <p>Uveal melanoma is the most common primary ocular neoplasm in adults. It is peculiar for its hematogenous dissemination and its high propensity to spread to the liver. Current treatments rarely prolong patient survival. We hypothesized that metastatic uveal melanoma cells modulate the function of surrounding hepatic stellate cells to facilitate their own growth and survival. This study was conducted to investigate the role of the hepatic microenvironment on uveal melanoma aggressiveness. We demonstrated that the paracrine signaling of surrounding hepatic stellate cells have more transcriptional impact on metastatic uveal melanoma cells. Upregulated transcripts were linked to inflammation and included several interleukins. The uveal melanoma-stellate cell crosstalk induced as well the expression of transmembrane integrins. In addition, the interleukin-6 receptor inhibitor Tocilizumab did not reduce the growth of uveal melanoma cells. Our results provide evidence that inflammatory mediators are key players in the homing of uveal melanoma cells to the liver. The bidirectional crosstalk between uveal melanoma cells and hepatic stellate cells involved pro-fibrogenic interleukins. The inflammatory characteristics of the metastatic microenvironment might offer relevant therapeutic opportunities in uveal melanoma.</p> </abstract> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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