Identification of truncated chemokine receptor 7 in human colorectal cancer unable to localize to the cell surface and unreactive to external ligands.
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.
Na
Il-Kang
IK
Hematology, Oncology and Transfusion Medicine, Charité-CBF, Hindenburgdamm 30, Berlin, Germany.
Busse
Antonia
A
Scheibenbogen
Carmen
C
Ghadjar
Pirus
P
Coupland
Sarah Ellen
SE
Letsch
Anne
A
Loddenkemper
Christoph
C
Stroux
Andrea
A
Bauer
Sandra
S
Thiel
Eckhard
E
Keilholz
Ulrich
U
D017398:Alternative Splicing; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism
C515370:CCR7 protein, human; D017931:DNA Primers; D008024:Ligands; D012333:RNA, Messenger; D054400:Receptors, CCR7; D004247:DNA