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Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets

BACKGROUND: Hepatocellular (HCC) and cholangiocellular carcinomas (CCC) display an exceptionally poor prognosis. Especially for advanced disease no efficient standard therapy is currently available. Recently, somatostatin analogs have been evaluated for the treatment of HCC, however, with contradict...

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Autores principales: Kaemmerer, Daniel, Schindler, Robin, Mußbach, Franziska, Dahmen, Uta, Altendorf-Hofmann, Annelore, Dirsch, Olaf, Sänger, Jörg, Schulz, Stefan, Lupp, Amelie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745780/
https://www.ncbi.nlm.nih.gov/pubmed/29282035
http://dx.doi.org/10.1186/s12885-017-3911-3
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author Kaemmerer, Daniel
Schindler, Robin
Mußbach, Franziska
Dahmen, Uta
Altendorf-Hofmann, Annelore
Dirsch, Olaf
Sänger, Jörg
Schulz, Stefan
Lupp, Amelie
author_facet Kaemmerer, Daniel
Schindler, Robin
Mußbach, Franziska
Dahmen, Uta
Altendorf-Hofmann, Annelore
Dirsch, Olaf
Sänger, Jörg
Schulz, Stefan
Lupp, Amelie
author_sort Kaemmerer, Daniel
collection PubMed
description BACKGROUND: Hepatocellular (HCC) and cholangiocellular carcinomas (CCC) display an exceptionally poor prognosis. Especially for advanced disease no efficient standard therapy is currently available. Recently, somatostatin analogs have been evaluated for the treatment of HCC, however, with contradictory results. Besides, for both malignancies the chemokine receptor CXCR4 has been discussed as a possible new target structure. METHODS: Expression of somatostatin receptor (SSTR) subtypes 1, 2A, 3, 4, and 5, and of CXCR4 was evaluated in a total of 71 HCCs and 27 CCCs by immunohistochemistry using well-characterized novel monoclonal antibodies. RESULTS: In HCC tumor cells, frequency and intensity of expression of SSTRs and CXCR4 were only low. CXCR4 was present in about 40% of the HCCs, although at a low intensity. SSTR5, SSTR2, and SSTR3 were detected in about 15%, 8%, and 5% of the HCC tumors, respectively. SSTR and CXCR4 expression was much higher in CCC than in HCC. CXCR4 and SSTR1 were present in 60% and 67% of the CCC samples, respectively, followed by SSTR2 and SSTR5, which were detected in 30% and 11% of the tumors, respectively. Most notably, CXCR4 was intensely expressed on the tumor capillaries in about 50% of the HCCs and CCCs. CXCR4 expression on tumor vessels was associated with poor patient outcomes. CONCLUSIONS: CCC, but not HCC, may be suitable for SSTR-based treatments. Because of the predominant expression of SSTR1, pan-somatostatin analogs should be preferred. In both HCC and CCC, indirect targeting of tumors via the CXCR4-positive tumor capillaries may represent a promising additional therapeutic strategy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3911-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-57457802018-01-03 Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets Kaemmerer, Daniel Schindler, Robin Mußbach, Franziska Dahmen, Uta Altendorf-Hofmann, Annelore Dirsch, Olaf Sänger, Jörg Schulz, Stefan Lupp, Amelie BMC Cancer Research Article BACKGROUND: Hepatocellular (HCC) and cholangiocellular carcinomas (CCC) display an exceptionally poor prognosis. Especially for advanced disease no efficient standard therapy is currently available. Recently, somatostatin analogs have been evaluated for the treatment of HCC, however, with contradictory results. Besides, for both malignancies the chemokine receptor CXCR4 has been discussed as a possible new target structure. METHODS: Expression of somatostatin receptor (SSTR) subtypes 1, 2A, 3, 4, and 5, and of CXCR4 was evaluated in a total of 71 HCCs and 27 CCCs by immunohistochemistry using well-characterized novel monoclonal antibodies. RESULTS: In HCC tumor cells, frequency and intensity of expression of SSTRs and CXCR4 were only low. CXCR4 was present in about 40% of the HCCs, although at a low intensity. SSTR5, SSTR2, and SSTR3 were detected in about 15%, 8%, and 5% of the HCC tumors, respectively. SSTR and CXCR4 expression was much higher in CCC than in HCC. CXCR4 and SSTR1 were present in 60% and 67% of the CCC samples, respectively, followed by SSTR2 and SSTR5, which were detected in 30% and 11% of the tumors, respectively. Most notably, CXCR4 was intensely expressed on the tumor capillaries in about 50% of the HCCs and CCCs. CXCR4 expression on tumor vessels was associated with poor patient outcomes. CONCLUSIONS: CCC, but not HCC, may be suitable for SSTR-based treatments. Because of the predominant expression of SSTR1, pan-somatostatin analogs should be preferred. In both HCC and CCC, indirect targeting of tumors via the CXCR4-positive tumor capillaries may represent a promising additional therapeutic strategy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3911-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-28 /pmc/articles/PMC5745780/ /pubmed/29282035 http://dx.doi.org/10.1186/s12885-017-3911-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kaemmerer, Daniel
Schindler, Robin
Mußbach, Franziska
Dahmen, Uta
Altendorf-Hofmann, Annelore
Dirsch, Olaf
Sänger, Jörg
Schulz, Stefan
Lupp, Amelie
Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
title Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
title_full Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
title_fullStr Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
title_full_unstemmed Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
title_short Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
title_sort somatostatin and cxcr4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745780/
https://www.ncbi.nlm.nih.gov/pubmed/29282035
http://dx.doi.org/10.1186/s12885-017-3911-3
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