LymphedemaV1, Main, Exploration, bibRecord, 003094

The G-protein Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis

Identifieur interne : 003094 ( Main/Exploration ); précédent : 003093; suivant : 003095

The G-protein Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis

Auteurs : Leonid L. Nikitenko [Royaume-Uni, Russie] ; Russell Leek ; Stephen Henderson [Royaume-Uni] ; Nischalan Pillay [Royaume-Uni] ; Helen Turley ; Daniele Generali [Italie] ; Sarah Gunningham [Nouvelle-Zélande] ; Helen R. Morrin [Nouvelle-Zélande] ; Andrea Pellagatti ; Margaret C. P. Rees [Royaume-Uni] ; Adrian L. Harris ; Stephen B. Fox [Australie]

Source :

Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2013.

RBID : PMC:3836221

Abstract

Purpose

The G-protein coupled receptor (GPCR) CLR and its ligand peptide adrenomedullin (AM, encoded by ADM gene) are implicated in tumor angiogenesis in mouse models but poorly defined in human cancers. We therefore investigated the diagnostic/prognostic utility for CLR in human tumor types that may rely on AM signaling and in clear cell renal cell carcinoma (RCC), a highly vascular tumor, in particular.

Experimental design

In silico gene expression messenger RNA profiling microarray study (n=168 tumors) and cancer profiling cDNA array hybridization (n=241 pairs of patient-matched tumor/normal tissue samples) were performed to analyze ADM mRNA expression in 13 tumor types. Immunohistochemistry on tissue microarrays containing patient-matched renal tumor/normal tissues (n=87 pairs) was performed to study CLR expression and its association with clinico-pathological parameters and disease outcome.

Results

ADM expression was significantly up-regulated only in RCC and endometrial adenocarcinoma compared with normal tissue counterparts (P<0.01). CLR was localized in tumor cells and vessels in RCC and up-regulated compared to patient-matched normal control kidney (P<0.001). Higher CLR expression was found in advanced stages (P<0.05), correlated with high tumor grade (P<0.01) and conferred shorter overall survival (P<0.01).

Conclusions

In human tissues ADM expression is up-regulated in cancer-type specific manner, implicating potential role for AM signaling in particular in RCC, where CLR localization suggests autocrine/paracrine mode for AM action within the tumor microenvironment. Our findings reveal previously unrecognised CLR up-regulation in an autocrine loop with AM in RCC with potential application for this GPCR as a target for future functional studies and drug development.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836221

DOI: 10.1158/1078-0432.CCR-13-1712
PubMed: 23969937
PubMed Central: 3836221

Affiliations:

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The G-protein Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis</title>
<author><name sortKey="Nikitenko, Leonid L" sort="Nikitenko, Leonid L" uniqKey="Nikitenko L" first="Leonid L." last="Nikitenko">Leonid L. Nikitenko</name>
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<author><name sortKey="Henderson, Stephen" sort="Henderson, Stephen" uniqKey="Henderson S" first="Stephen" last="Henderson">Stephen Henderson</name>
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<region type="région" nuts="1">Grand Londres</region>
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<author><name sortKey="Pillay, Nischalan" sort="Pillay, Nischalan" uniqKey="Pillay N" first="Nischalan" last="Pillay">Nischalan Pillay</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Sarcoma Biology Group , UCL Cancer Institute, University College London, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
<settlement type="city">Londres</settlement>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
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<author><name sortKey="Turley, Helen" sort="Turley, Helen" uniqKey="Turley H" first="Helen" last="Turley">Helen Turley</name>
<affiliation><nlm:aff id="A5">Nuffield Department of Clinical Laboratory Sciences, Weatherall Institute of Molecular Medicine</nlm:aff>
<wicri:noCountry code="subfield">Weatherall Institute of Molecular Medicine</wicri:noCountry>
</affiliation>
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<author><name sortKey="Generali, Daniele" sort="Generali, Daniele" uniqKey="Generali D" first="Daniele" last="Generali">Daniele Generali</name>
<affiliation><nlm:aff id="A7">Cancer Research UK Oncology Laboratory, Weatherall Institute of Molecular Medicine</nlm:aff>
<wicri:noCountry code="subfield">Weatherall Institute of Molecular Medicine</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Unità di Patologia Mammaria Senologia e Breast Unit Centro di Medicina Molecolare Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Unità di Patologia Mammaria Senologia e Breast Unit Centro di Medicina Molecolare Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona</wicri:regionArea>
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</affiliation>
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<author><name sortKey="Gunningham, Sarah" sort="Gunningham, Sarah" uniqKey="Gunningham S" first="Sarah" last="Gunningham">Sarah Gunningham</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Department of Pathology, University of Otago, Christchurch 8140, New Zealand</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Department of Pathology, University of Otago, Christchurch 8140</wicri:regionArea>
<wicri:noRegion>Christchurch 8140</wicri:noRegion>
</affiliation>
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<author><name sortKey="Morrin, Helen R" sort="Morrin, Helen R" uniqKey="Morrin H" first="Helen R." last="Morrin">Helen R. Morrin</name>
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<country xml:lang="fr">Nouvelle-Zélande</country>
<wicri:regionArea>Cancer Society Tissue Bank, University of Otago, Christchurch 8140</wicri:regionArea>
<wicri:noRegion>Christchurch 8140</wicri:noRegion>
</affiliation>
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<author><name sortKey="Pellagatti, Andrea" sort="Pellagatti, Andrea" uniqKey="Pellagatti A" first="Andrea" last="Pellagatti">Andrea Pellagatti</name>
<affiliation><nlm:aff id="A5">Nuffield Department of Clinical Laboratory Sciences, Weatherall Institute of Molecular Medicine</nlm:aff>
<wicri:noCountry code="subfield">Weatherall Institute of Molecular Medicine</wicri:noCountry>
</affiliation>
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<author><name sortKey="Rees, Margaret C P" sort="Rees, Margaret C P" uniqKey="Rees M" first="Margaret C. P." last="Rees">Margaret C. P. Rees</name>
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<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Nuffield Department of Obstetrics and Gynaecology; University of Oxford, John Radcliffe Hospital, Oxford</wicri:regionArea>
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<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
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<author><name sortKey="Harris, Adrian L" sort="Harris, Adrian L" uniqKey="Harris A" first="Adrian L." last="Harris">Adrian L. Harris</name>
<affiliation><nlm:aff id="A7">Cancer Research UK Oncology Laboratory, Weatherall Institute of Molecular Medicine</nlm:aff>
<wicri:noCountry code="subfield">Weatherall Institute of Molecular Medicine</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Fox, Stephen B" sort="Fox, Stephen B" uniqKey="Fox S" first="Stephen B." last="Fox">Stephen B. Fox</name>
<affiliation><nlm:aff id="A12">Department of Pathology, University of Melbourne, Parkville, VIC, 3010</nlm:aff>
<wicri:noCountry code="subfield">3010</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A13">Department of Pathology, Peter MacCallum Cancer Centre, VIC, 3002, Melbourne, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>Department of Pathology, Peter MacCallum Cancer Centre, VIC, 3002, Melbourne</wicri:regionArea>
<wicri:noRegion>Melbourne</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title>
<idno type="ISSN">1078-0432</idno>
<imprint><date when="2013">2013</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title>
<p id="P1">The G-protein coupled receptor (GPCR) CLR and its ligand peptide adrenomedullin (AM, encoded by <italic>ADM</italic>
 gene) are implicated in tumor angiogenesis in mouse models but poorly defined in human cancers. We therefore investigated the diagnostic/prognostic utility for CLR in human tumor types that may rely on AM signaling and in clear cell renal cell carcinoma (RCC), a highly vascular tumor, in particular.</p>
</sec>
<sec id="S2"><title>Experimental design</title>
<p id="P2"><italic>In silico</italic>
 gene expression messenger RNA profiling microarray study (n=168 tumors) and cancer profiling cDNA array hybridization (n=241 pairs of patient-matched tumor/normal tissue samples) were performed to analyze <italic>ADM</italic>
 mRNA expression in 13 tumor types. Immunohistochemistry on tissue microarrays containing patient-matched renal tumor/normal tissues (n=87 pairs) was performed to study CLR expression and its association with clinico-pathological parameters and disease outcome.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3"><italic>ADM</italic>
 expression was significantly up-regulated only in RCC and endometrial adenocarcinoma compared with normal tissue counterparts (P<0.01). CLR was localized in tumor cells and vessels in RCC and up-regulated compared to patient-matched normal control kidney (P<0.001). Higher CLR expression was found in advanced stages (P<0.05), correlated with high tumor grade (P<0.01) and conferred shorter overall survival (P<0.01).</p>
</sec>
<sec id="S4"><title>Conclusions</title>
<p id="P4">In human tissues <italic>ADM</italic>
 expression is up-regulated in cancer-type specific manner, implicating potential role for AM signaling in particular in RCC, where CLR localization suggests autocrine/paracrine mode for AM action within the tumor microenvironment. Our findings reveal previously unrecognised CLR up-regulation in an autocrine loop with AM in RCC with potential application for this GPCR as a target for future functional studies and drug development.</p>
</sec>
</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Italie</li>
<li>Nouvelle-Zélande</li>
<li>Royaume-Uni</li>
<li>Russie</li>
</country>
<region><li>Angleterre</li>
<li>Grand Londres</li>
<li>Oxfordshire</li>
</region>
<settlement><li>Londres</li>
<li>Oxford</li>
</settlement>
<orgName><li>University College de Londres</li>
<li>Université d'Oxford</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Harris, Adrian L" sort="Harris, Adrian L" uniqKey="Harris A" first="Adrian L." last="Harris">Adrian L. Harris</name>
<name sortKey="Leek, Russell" sort="Leek, Russell" uniqKey="Leek R" first="Russell" last="Leek">Russell Leek</name>
<name sortKey="Pellagatti, Andrea" sort="Pellagatti, Andrea" uniqKey="Pellagatti A" first="Andrea" last="Pellagatti">Andrea Pellagatti</name>
<name sortKey="Turley, Helen" sort="Turley, Helen" uniqKey="Turley H" first="Helen" last="Turley">Helen Turley</name>
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<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Nikitenko, Leonid L" sort="Nikitenko, Leonid L" uniqKey="Nikitenko L" first="Leonid L." last="Nikitenko">Leonid L. Nikitenko</name>
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<name sortKey="Henderson, Stephen" sort="Henderson, Stephen" uniqKey="Henderson S" first="Stephen" last="Henderson">Stephen Henderson</name>
<name sortKey="Nikitenko, Leonid L" sort="Nikitenko, Leonid L" uniqKey="Nikitenko L" first="Leonid L." last="Nikitenko">Leonid L. Nikitenko</name>
<name sortKey="Nikitenko, Leonid L" sort="Nikitenko, Leonid L" uniqKey="Nikitenko L" first="Leonid L." last="Nikitenko">Leonid L. Nikitenko</name>
<name sortKey="Pillay, Nischalan" sort="Pillay, Nischalan" uniqKey="Pillay N" first="Nischalan" last="Pillay">Nischalan Pillay</name>
<name sortKey="Rees, Margaret C P" sort="Rees, Margaret C P" uniqKey="Rees M" first="Margaret C. P." last="Rees">Margaret C. P. Rees</name>
</country>
<country name="Russie"><noRegion><name sortKey="Nikitenko, Leonid L" sort="Nikitenko, Leonid L" uniqKey="Nikitenko L" first="Leonid L." last="Nikitenko">Leonid L. Nikitenko</name>
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<country name="Italie"><noRegion><name sortKey="Generali, Daniele" sort="Generali, Daniele" uniqKey="Generali D" first="Daniele" last="Generali">Daniele Generali</name>
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<country name="Nouvelle-Zélande"><noRegion><name sortKey="Gunningham, Sarah" sort="Gunningham, Sarah" uniqKey="Gunningham S" first="Sarah" last="Gunningham">Sarah Gunningham</name>
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<name sortKey="Morrin, Helen R" sort="Morrin, Helen R" uniqKey="Morrin H" first="Helen R." last="Morrin">Helen R. Morrin</name>
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<country name="Australie"><noRegion><name sortKey="Fox, Stephen B" sort="Fox, Stephen B" uniqKey="Fox S" first="Stephen B." last="Fox">Stephen B. Fox</name>
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</record>

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{{Explor lien
   |wiki=    Wicri/Sante
   |area=    LymphedemaV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:3836221
   |texte=   The G-protein Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis
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This area was generated with Dilib version V0.6.31.
Data generation: Sat Nov 4 17:40:35 2017. Site generation: Tue Feb 13 16:42:16 2024

Serveur d'exploration sur le lymphœdème

The G-protein Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis

The G-protein Coupled Receptor CLR is Up-regulated in an Autocrine Loop with Adrenomedullin in Clear Cell Renal Cell Carcinoma and Associated with Poor Prognosis

Source :

Abstract

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	Serveur d'exploration sur le lymphœdème
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