Apelin promotes lymphangiogenesis and lymph node metastasis
Identifieur interne : 002D44 ( Main/Curation ); précédent : 002D43; suivant : 002D45Apelin promotes lymphangiogenesis and lymph node metastasis
Auteurs : Judit Berta [Autriche, Hongrie] ; Mir Alireza Hoda [Autriche] ; Viktoria Laszlo [Autriche, Hongrie] ; Anita Rozsas [Autriche, Hongrie] ; Tamas Garay [Hongrie] ; Szilvia Torok [Hongrie] ; Michael Grusch [Autriche] ; Walter Berger [Autriche] ; Sandor Paku [Hongrie] ; Ferenc Renyi-Vamos [Autriche, Hongrie] ; Bernard Masri [France] ; Jozsef Tovari ; Marion Groger [Autriche] ; Walter Klepetko [Autriche] ; Balazs Hegedus [Autriche, Hongrie] ; Balazs Dome [Autriche, Hongrie]Source :
- Oncotarget [ 1949-2553 ] ; 2014.
Abstract
Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs
Url:
PubMed: 24962866
PubMed Central: 4147335
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Jozsef Tovari<affiliation><nlm:aff id="A9"> Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary; Skin and Endothelium Research Division (SERD)</nlm:aff>
<wicri:noCountry code="subfield">Hungary; Skin and Endothelium Research Division (SERD)</wicri:noCountry>
</affiliation>
Le document en format XML
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<affiliation wicri:level="3"><nlm:aff id="A6"> 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea> 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Renyi Vamos, Ferenc" sort="Renyi Vamos, Ferenc" uniqKey="Renyi Vamos F" first="Ferenc" last="Renyi-Vamos">Ferenc Renyi-Vamos</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna</wicri:regionArea>
<wicri:noRegion>Medical University of Vienna</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A7"> Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea> Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Masri, Bernard" sort="Masri, Bernard" uniqKey="Masri B" first="Bernard" last="Masri">Bernard Masri</name>
<affiliation wicri:level="3"><nlm:aff id="A8"> Cancer Research Center of Toulouse, INSERM U1037-Université Paul Sabatier Toulouse III, Toulouse, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea> Cancer Research Center of Toulouse, INSERM U1037-Université Paul Sabatier Toulouse III, Toulouse</wicri:regionArea>
<placeName><region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tovari, Jozsef" sort="Tovari, Jozsef" uniqKey="Tovari J" first="Jozsef" last="Tovari">Jozsef Tovari</name>
<affiliation><nlm:aff id="A9"> Department of Experimental Pharmacology, National Institute of Oncology, Budapest, Hungary; Skin and Endothelium Research Division (SERD)</nlm:aff>
<wicri:noCountry code="subfield">Hungary; Skin and Endothelium Research Division (SERD)</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Groger, Marion" sort="Groger, Marion" uniqKey="Groger M" first="Marion" last="Groger">Marion Groger</name>
<affiliation wicri:level="1"><nlm:aff id="A10"> Department of Dermatology, Medical University of Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea> Department of Dermatology, Medical University of Vienna</wicri:regionArea>
<wicri:noRegion>Medical University of Vienna</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A11"> Core Facility Imaging, Core Facilities, Medical University of Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea> Core Facility Imaging, Core Facilities, Medical University of Vienna</wicri:regionArea>
<wicri:noRegion>Medical University of Vienna</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Klepetko, Walter" sort="Klepetko, Walter" uniqKey="Klepetko W" first="Walter" last="Klepetko">Walter Klepetko</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna</wicri:regionArea>
<wicri:noRegion>Medical University of Vienna</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hegedus, Balazs" sort="Hegedus, Balazs" uniqKey="Hegedus B" first="Balazs" last="Hegedus">Balazs Hegedus</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna</wicri:regionArea>
<wicri:noRegion>Medical University of Vienna</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A4"> MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea> MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="A12">** These authors share last authorship</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dome, Balazs" sort="Dome, Balazs" uniqKey="Dome B" first="Balazs" last="Dome">Balazs Dome</name>
<affiliation wicri:level="1"><nlm:aff id="A1"> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea> Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna</wicri:regionArea>
<wicri:noRegion>Medical University of Vienna</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea> Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A7"> Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea> Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="A12">** These authors share last authorship</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Oncotarget</title>
<idno type="eISSN">1949-2553</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>Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs <italic>in vitro</italic>
, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their <italic>in vitro</italic>
capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels <italic>in vivo</italic>
in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated <italic>in vivo</italic>
tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis.</p>
</div>
</front>
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