Identification of truncated chemokine receptor 7 in human colorectal cancer unable to localize to the cell surface and unreactive to external ligands
Il-Kang Na
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorAntonia Busse
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorCarmen Scheibenbogen
Institute of Medical Immunology, Charité - CCM, Schumannstr. 20/21, Berlin, Germany
Search for more papers by this authorPirus Ghadjar
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorSarah Ellen Coupland
Institute for Pathology, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Department of Cellular and Molecular Pathology University of Liverpool, Liverpool, United Kingdom
Search for more papers by this authorAnne Letsch
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorChristoph Loddenkemper
Institute for Pathology, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Charité Research Center ImmunoSciences, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorAndrea Stroux
Institute for Medical Informatics, Biometry, and Epidemiology, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorSandra Bauer
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorEckhard Thiel
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorCorresponding Author
Ulrich Keilholz
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Fax: +49-30-8445-4021
Department of Medicine III, Hematology/Oncology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12200, GermanySearch for more papers by this authorIl-Kang Na
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorAntonia Busse
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorCarmen Scheibenbogen
Institute of Medical Immunology, Charité - CCM, Schumannstr. 20/21, Berlin, Germany
Search for more papers by this authorPirus Ghadjar
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorSarah Ellen Coupland
Institute for Pathology, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Department of Cellular and Molecular Pathology University of Liverpool, Liverpool, United Kingdom
Search for more papers by this authorAnne Letsch
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorChristoph Loddenkemper
Institute for Pathology, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Charité Research Center ImmunoSciences, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorAndrea Stroux
Institute for Medical Informatics, Biometry, and Epidemiology, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorSandra Bauer
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorEckhard Thiel
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Search for more papers by this authorCorresponding Author
Ulrich Keilholz
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany
Fax: +49-30-8445-4021
Department of Medicine III, Hematology/Oncology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12200, GermanySearch for more papers by this authorAbstract
Chemokine receptors are thought to be involved in the process of cancer metastases. When investigating cell lines and tissues from colorectal cancer (CRC), the CCR7 protein unexpectedly was confined to the cytoplasm and not present on the cell surface. This study investigated at the DNA, mRNA and protein level, the mechanism and the consequences of the failure of CCR7 to localize to the cell membrane. In all 15 CRC cell lines tested, no surface CCR7 was detected and no chemotactic response was elicited upon in-vitro exposure to CCR7 chemokine ligands (CCL) 19 and CCL21. Integrity of CCR7 DNA and mRNA was examined with respect to signal peptide expression in cell lines and CRC tissues by real-time RT-PCR and sequencing. Nine of 15 CRC cell lines and 8 of 14 CRC tissues revealed a truncated CCR7 mRNA species containing various incomplete signal peptide encoding sequences, while the corresponding DNA was intact. These results indicate in CRC frequent alternative splicing or post-transcriptional mRNA modification resulting in a CCR7 molecule lacking an intact signal peptide prohibiting membrane translocation. Further studies would be necessary to identify a potential intracellular role of the truncated CCR7, abundantly present in the cytoplasm. © 2008 Wiley-Liss, Inc.
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