Endothelial transdifferentiation in hepatocellular carcinoma: loss of Stabilin‐2 expression in peri‐tumourous liver correlates with increased survival
Identifieur interne : 000160 ( Main/Exploration ); précédent : 000159; suivant : 000161Endothelial transdifferentiation in hepatocellular carcinoma: loss of Stabilin‐2 expression in peri‐tumourous liver correlates with increased survival
Auteurs : Cyrill Géraud [Allemagne] ; Carolin Mogler [Allemagne] ; Anja Runge [Allemagne] ; Konstantin Evdokimov [Allemagne] ; Shun Lu [Allemagne] ; Kai Schledzewski [Allemagne] ; Bernd Arnold [Allemagne] ; Günter H Mmerling [Allemagne] ; Philipp S. Koch [Allemagne] ; Kai Breuhahn [Allemagne] ; Thomas Longerich [Allemagne] ; Alexander Marx [Allemagne] ; Christel Weiss [Allemagne] ; Friederike Damm [Allemagne] ; Astrid Schmieder [Allemagne] ; Peter Schirmacher [Allemagne] ; Hellmut G. Augustin [Allemagne] ; Sergij Goerdt [Allemagne]Source :
- Liver International [ 1478-3223 ] ; 2013-10.
English descriptors
- Teeft :
- Adhesion, Angiogenesis, Angiogenic, Angiogenic switch, Carcinoma, Different animals, Dysplastic nodules, Endothelial, Endothelial cells, Endothelial expression, Endothelial transdifferentiation, Endothelium, Healthy liver tissue, Heidelberg, Heidelberg university, Hepatic, Hepatocellular, Hepatocellular carcinoma, Human hepatocellular carcinoma, Human hepatocellular carcinomas, Inducible, Intussusceptive angiogenesis, John wiley sons, Large nodules, Liver, Liver sinusoids, Liver tissue, Liver tumours, Lsec, Lsec marker protein expression, Lsec marker proteins, Macrophage, Mannheim, Marker, Marker expression, Marker proteins, Medical faculty mannheim, Microarray, Microvascular invasion, Murine, Murine hepatocellular tumours, Negative samples, Nodule, Nodule size, Normal lsec, Overall survival, Pathol, Receptor, Sinusoid, Small nodules, Tissue microarray, Tissue microarrays, Tissue samples, Transdifferentiation, Treatment modalities, Tumour, Tumour endothelium, Tumour nodules, Tumour vessels, Tumourous, Tumourous tissue, Vascular, Vascular abnormalization, Vascular remodelling.
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumour that is characterized by extensive vascular remodelling and responsiveness to treatment with the anti‐angiogenic multikinase inhibitor sorafenib. The aim was to study endothelial remodelling in HCC.
The murine inducible albumin‐SV40‐large T‐antigen model and two tissue microarrays (TMA) with 295 tumourous and 83 peri‐tumourous samples of 296 patients with HCC were analysed for expression of liver sinusoidal endothelial cell (LSEC)‐specific marker proteins, stabilin‐1 and stabilin‐2, LYVE‐1 and CD32b.
LSEC marker proteins were sequentially lost during HCC progression in the murine HCC model being absent from tumour nodules larger than 800 μm in diameter. Similarly, the TMA analysis of human HCCs revealed loss of all four marker proteins in the majority of tumourous tissue samples. Preservation of LYVE‐1 expression showed a significant correlation with low grading (G1). In corresponding peri‐tumourous liver tissue, loss of all marker proteins was seen in a minor proportion of cases (34%) while the majority of cases retained expression of at least one of the marker proteins. Loss of stabilin‐2 expression in peri‐tumourous liver tissue of patients with HCC was significantly less likely to occur (38%) than loss of the other marker proteins (63–95%) and it was associated with significantly longer tumour‐specific (P = 0.0523) and overall (P = 0.0338) survival. Loss of stabilin‐2 may enhance survival in HCC by preventing endothelial‐tumour cell adhesive interactions and microvascular invasion.
In summary, endothelial transdifferentiation is a major pathogenic event in HCC development indicating a switch from vessel co‐option/intussusceptive angiogenesis to sprouting angiogenesis.
Url:
DOI: 10.1111/liv.12262
Affiliations:
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sort="Lu, Shun" uniqKey="Lu S" first="Shun" last="Lu">Shun Lu</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Schledzewski, Kai" sort="Schledzewski, Kai" uniqKey="Schledzewski K" first="Kai" last="Schledzewski">Kai Schledzewski</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, 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xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Koch, Philipp S" sort="Koch, Philipp S" uniqKey="Koch P" first="Philipp S." last="Koch">Philipp S. Koch</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Breuhahn, Kai" sort="Breuhahn, Kai" uniqKey="Breuhahn K" first="Kai" last="Breuhahn">Kai Breuhahn</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, University Clinic Heidelberg, Heidelberg University, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Longerich, Thomas" sort="Longerich, Thomas" uniqKey="Longerich T" first="Thomas" last="Longerich">Thomas Longerich</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, University Clinic Heidelberg, Heidelberg University, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Marx, Alexander" sort="Marx, Alexander" uniqKey="Marx A" first="Alexander" last="Marx">Alexander Marx</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pathology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Weiss, Christel" sort="Weiss, Christel" uniqKey="Weiss C" first="Christel" last="Weiss">Christel Weiss</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division for Medical Statistics, Medical Faculty Mannheim, Heidelberg University, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Damm, Friederike" sort="Damm, Friederike" uniqKey="Damm F" first="Friederike" last="Damm">Friederike Damm</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Schmieder, Astrid" sort="Schmieder, Astrid" uniqKey="Schmieder A" first="Astrid" last="Schmieder">Astrid Schmieder</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author><author><name sortKey="Schirmacher, Peter" sort="Schirmacher, Peter" uniqKey="Schirmacher P" first="Peter" last="Schirmacher">Peter Schirmacher</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Pathology, University Clinic Heidelberg, Heidelberg University, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Joint Research Division of Vascular Biology, Medical Faculty Mannheim, Heidelberg University, and German Cancer Research Center Heidelberg, Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Goerdt, Sergij" sort="Goerdt, Sergij" uniqKey="Goerdt S" first="Sergij" last="Goerdt">Sergij Goerdt</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, and Center of Excellence in Dermatology, Mannheim</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Mannheim</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Liver International</title><title level="j" type="abbrev">Liver Int</title><idno type="ISSN">1478-3223</idno><idno type="eISSN">1478-3231</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-10">2013-10</date><biblScope unit="volume">33</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1428">1428</biblScope><biblScope unit="page" to="1440">1440</biblScope></imprint><idno type="ISSN">1478-3223</idno></series><idno type="istex">4A5D211E0BD624625218986867B036F783D3B375</idno><idno type="DOI">10.1111/liv.12262</idno><idno type="ArticleID">LIV12262</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1478-3223</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Adhesion</term><term>Angiogenesis</term><term>Angiogenic</term><term>Angiogenic switch</term><term>Carcinoma</term><term>Different animals</term><term>Dysplastic nodules</term><term>Endothelial</term><term>Endothelial cells</term><term>Endothelial expression</term><term>Endothelial transdifferentiation</term><term>Endothelium</term><term>Healthy liver tissue</term><term>Heidelberg</term><term>Heidelberg university</term><term>Hepatic</term><term>Hepatocellular</term><term>Hepatocellular carcinoma</term><term>Human hepatocellular carcinoma</term><term>Human hepatocellular carcinomas</term><term>Inducible</term><term>Intussusceptive angiogenesis</term><term>John wiley sons</term><term>Large nodules</term><term>Liver</term><term>Liver sinusoids</term><term>Liver tissue</term><term>Liver tumours</term><term>Lsec</term><term>Lsec marker protein expression</term><term>Lsec marker proteins</term><term>Macrophage</term><term>Mannheim</term><term>Marker</term><term>Marker expression</term><term>Marker proteins</term><term>Medical faculty mannheim</term><term>Microarray</term><term>Microvascular invasion</term><term>Murine</term><term>Murine hepatocellular tumours</term><term>Negative samples</term><term>Nodule</term><term>Nodule size</term><term>Normal lsec</term><term>Overall survival</term><term>Pathol</term><term>Receptor</term><term>Sinusoid</term><term>Small nodules</term><term>Tissue microarray</term><term>Tissue microarrays</term><term>Tissue samples</term><term>Transdifferentiation</term><term>Treatment modalities</term><term>Tumour</term><term>Tumour endothelium</term><term>Tumour nodules</term><term>Tumour vessels</term><term>Tumourous</term><term>Tumourous tissue</term><term>Vascular</term><term>Vascular abnormalization</term><term>Vascular remodelling</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Hepatocellular carcinoma (HCC) is a malignant tumour that is characterized by extensive vascular remodelling and responsiveness to treatment with the anti‐angiogenic multikinase inhibitor sorafenib. The aim was to study endothelial remodelling in HCC.</div><div type="abstract">The murine inducible albumin‐SV40‐large T‐antigen model and two tissue microarrays (TMA) with 295 tumourous and 83 peri‐tumourous samples of 296 patients with HCC were analysed for expression of liver sinusoidal endothelial cell (LSEC)‐specific marker proteins, stabilin‐1 and stabilin‐2, LYVE‐1 and CD32b.</div><div type="abstract">LSEC marker proteins were sequentially lost during HCC progression in the murine HCC model being absent from tumour nodules larger than 800 μm in diameter. Similarly, the TMA analysis of human HCCs revealed loss of all four marker proteins in the majority of tumourous tissue samples. Preservation of LYVE‐1 expression showed a significant correlation with low grading (G1). In corresponding peri‐tumourous liver tissue, loss of all marker proteins was seen in a minor proportion of cases (34%) while the majority of cases retained expression of at least one of the marker proteins. Loss of stabilin‐2 expression in peri‐tumourous liver tissue of patients with HCC was significantly less likely to occur (38%) than loss of the other marker proteins (63–95%) and it was associated with significantly longer tumour‐specific (P = 0.0523) and overall (P = 0.0338) survival. Loss of stabilin‐2 may enhance survival in HCC by preventing endothelial‐tumour cell adhesive interactions and microvascular invasion.</div><div type="abstract">In summary, endothelial transdifferentiation is a major pathogenic event in HCC development indicating a switch from vessel co‐option/intussusceptive angiogenesis to sprouting angiogenesis.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bade-Wurtemberg</li><li>District de Karlsruhe</li></region><settlement><li>Heidelberg</li><li>Mannheim</li></settlement></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Geraud, Cyrill" sort="Geraud, Cyrill" uniqKey="Geraud C" first="Cyrill" last="Géraud">Cyrill Géraud</name></region><name sortKey="Arnold, Bernd" sort="Arnold, Bernd" uniqKey="Arnold B" first="Bernd" last="Arnold">Bernd Arnold</name><name sortKey="Augustin, Hellmut G" sort="Augustin, Hellmut G" uniqKey="Augustin H" first="Hellmut G." last="Augustin">Hellmut G. Augustin</name><name sortKey="Breuhahn, Kai" sort="Breuhahn, Kai" uniqKey="Breuhahn K" first="Kai" last="Breuhahn">Kai Breuhahn</name><name sortKey="Damm, Friederike" sort="Damm, Friederike" uniqKey="Damm F" first="Friederike" last="Damm">Friederike Damm</name><name sortKey="Evdokimov, Konstantin" sort="Evdokimov, Konstantin" uniqKey="Evdokimov K" first="Konstantin" last="Evdokimov">Konstantin Evdokimov</name><name sortKey="Geraud, Cyrill" sort="Geraud, Cyrill" uniqKey="Geraud C" first="Cyrill" last="Géraud">Cyrill Géraud</name><name sortKey="Goerdt, Sergij" sort="Goerdt, Sergij" uniqKey="Goerdt S" first="Sergij" last="Goerdt">Sergij Goerdt</name><name sortKey="H Mmerling, Gunter" sort="H Mmerling, Gunter" uniqKey="H Mmerling G" first="Günter" last="H Mmerling">Günter H Mmerling</name><name sortKey="Koch, Philipp S" sort="Koch, Philipp S" uniqKey="Koch P" first="Philipp S." last="Koch">Philipp S. Koch</name><name sortKey="Longerich, Thomas" sort="Longerich, Thomas" uniqKey="Longerich T" first="Thomas" last="Longerich">Thomas Longerich</name><name sortKey="Lu, Shun" sort="Lu, Shun" uniqKey="Lu S" first="Shun" last="Lu">Shun Lu</name><name sortKey="Marx, Alexander" sort="Marx, Alexander" uniqKey="Marx A" first="Alexander" last="Marx">Alexander Marx</name><name sortKey="Mogler, Carolin" sort="Mogler, Carolin" uniqKey="Mogler C" first="Carolin" last="Mogler">Carolin Mogler</name><name sortKey="Runge, Anja" sort="Runge, Anja" uniqKey="Runge A" first="Anja" last="Runge">Anja Runge</name><name sortKey="Schirmacher, Peter" sort="Schirmacher, Peter" uniqKey="Schirmacher P" first="Peter" last="Schirmacher">Peter Schirmacher</name><name sortKey="Schledzewski, Kai" sort="Schledzewski, Kai" uniqKey="Schledzewski K" first="Kai" last="Schledzewski">Kai Schledzewski</name><name sortKey="Schmieder, Astrid" sort="Schmieder, Astrid" uniqKey="Schmieder A" first="Astrid" last="Schmieder">Astrid Schmieder</name><name sortKey="Weiss, Christel" sort="Weiss, Christel" uniqKey="Weiss C" first="Christel" last="Weiss">Christel Weiss</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|étape= Exploration
|type= RBID
|clé= ISTEX:4A5D211E0BD624625218986867B036F783D3B375
|texte= Endothelial transdifferentiation in hepatocellular carcinoma: loss of Stabilin‐2 expression in peri‐tumourous liver correlates with increased survival
}}
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