Cargando…

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells

BACKGROUND: Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with...

Descripción completa

Detalles Bibliográficos
Autores principales: Rubie, Claudia, Frick , Vilma O, Ghadjar, Pirus, Wagner, Mathias, Justinger, Christoph, Faust, Sabrina K, Vicinus, Benjamin, Gräber, Stefan, Kollmar, Otto, Schilling, Martin K
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049756/
https://www.ncbi.nlm.nih.gov/pubmed/21349176
http://dx.doi.org/10.1186/1479-5876-9-22
_version_ 1782199267922804736
author Rubie, Claudia
Frick , Vilma O
Ghadjar, Pirus
Wagner, Mathias
Justinger, Christoph
Faust, Sabrina K
Vicinus, Benjamin
Gräber, Stefan
Kollmar, Otto
Schilling, Martin K
author_facet Rubie, Claudia
Frick , Vilma O
Ghadjar, Pirus
Wagner, Mathias
Justinger, Christoph
Faust, Sabrina K
Vicinus, Benjamin
Gräber, Stefan
Kollmar, Otto
Schilling, Martin K
author_sort Rubie, Claudia
collection PubMed
description BACKGROUND: Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition. METHODS: Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies. RESULTS: In CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05). CONCLUSIONS: CXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions.
format Text
id pubmed-3049756
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-30497562011-03-08 CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells Rubie, Claudia Frick , Vilma O Ghadjar, Pirus Wagner, Mathias Justinger, Christoph Faust, Sabrina K Vicinus, Benjamin Gräber, Stefan Kollmar, Otto Schilling, Martin K J Transl Med Research BACKGROUND: Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition. METHODS: Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29). Migration assays were performed after stimulation with CXCL12 and CXCR4 was inhibited by siRNA and neutralizing antibodies. RESULTS: In CRC tissues CXCL12 was significantly down-regulated and CXCR4 was significantly up-regulated compared to the corresponding normal tissues. In cell lines CXCR4 was predominantly expressed in SW480 and less pronounced in HT-29 cells. CXCL12 was only detectable in Caco-2 cells. CXCL12 stimulation had no impact on Caco-2 cells but significantly increased migration of CXCR4 bearing SW480 and HT-29 cells. This effect was significantly abrogated by neutralizing anti-CXCR4 antibody as well as by CXCR4 siRNAs (P < 0.05). CONCLUSIONS: CXCR4 expression was up-regulated in CRC and CXCL12 stimulation increased migration in CXCR4 bearing cell lines. Migration was inhibited by both neutralizing CXCR4 antibodies and CXCR4 siRNAs. Thus, the expression and functionality of CXCR4 might be associated with the metastatic potential of CRC cells and CXCL12/CXCR4 interactions might therefore constitute a promising target for specific treatment interventions. BioMed Central 2011-02-24 /pmc/articles/PMC3049756/ /pubmed/21349176 http://dx.doi.org/10.1186/1479-5876-9-22 Text en Copyright ©2011 Rubie et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Rubie, Claudia
Frick , Vilma O
Ghadjar, Pirus
Wagner, Mathias
Justinger, Christoph
Faust, Sabrina K
Vicinus, Benjamin
Gräber, Stefan
Kollmar, Otto
Schilling, Martin K
CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells
title CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells
title_full CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells
title_fullStr CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells
title_full_unstemmed CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells
title_short CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells
title_sort cxc receptor-4 mrna silencing abrogates cxcl12-induced migration of colorectal cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049756/
https://www.ncbi.nlm.nih.gov/pubmed/21349176
http://dx.doi.org/10.1186/1479-5876-9-22
work_keys_str_mv AT rubieclaudia cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT frickvilmao cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT ghadjarpirus cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT wagnermathias cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT justingerchristoph cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT faustsabrinak cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT vicinusbenjamin cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT graberstefan cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT kollmarotto cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells
AT schillingmartink cxcreceptor4mrnasilencingabrogatescxcl12inducedmigrationofcolorectalcancercells