CXCR7, formerly called RDC1 is a recently deorphanized G-protein coupled receptor which binds with high affinity the inflammatory and homing chemokines CXCL11/ITAC and CXCL12/SDF-1. Several reports have recently documented that CXCR7 promotes growth of tumors formed from breast and lung cancer cells and enhances experimental lung metastases in immunodeficient as well as immunocompetent mouse models of cancer. These effects did not depend on expression of the related receptor CXCR4. However, a new interesting finding from earlier microarray data of selection of invasive and metastatic expression patterns from two human lung adenocarcinoma cell lines, CL1-0 and CL1-5, indicated that up-regulation of CXCR7 appeared in low invasive and metastatic cells (CL1-0) but not in high invasive and metastatic cells (CL1-5). Therefore, it has the potential puzzle for the role of CXCR7 in human lung cancer progression. The purpose of this study is to investigate the impact of CXCR7 in human lung cancer progression. Our results from RT-PCR (reverse transcription-polymerase chain reaction) and western blotting assays confirmed that the levels of CXCR7 expression decreased as the tumors become more aggressive. The human lung adenocarcinoma cell line with high invasiveness and metastasis, CL1-5, had lower expression of CXCR7 than the CL1-0 cells, which is the low invasive and metastatic subpopulation. To investigate the role of CXCR7 in lung cancer progression, we used lentiviral vectors to stably and specifically knock down CXCR7 in CL1-0 cells and over-express CXCR7 in CL1-5 cells. Knockdown and over-expression of CXCR7 induced inverse expression of CXCR4 in protein levels. In vitro proliferation assay, migration assay and invasion assay showed that knock down of CXCR7 expression in CL1-0 cells promoted their proliferation, migration and invasion activities but over-expression of CXCR7 expression in CL1-5 cells suppressed these activities. These results differ from those in a previous report on murine lung cancer cells. Our data suggest that the CXCR7 plays a potential tumor suppresser in human lung adenocarcinoma cells and its mechanism may inhibit CXCR4 expression and its downstream signaling.
