CXCR7 as a chemokine receptor for SDF-1 promotes gastric cancer progression via MAPK pathways.

OBJECTIVE: As the alternate receptor for stromal cell-derived factor-1 (SDF-1) except CXCR4, CXCR7 has been shown to be involved in the progression of some malignancies. However, the role of SDF-1/CXCR7 in gastric cancer (GC) remains unclear.

MATERIALS AND METHODS: CXCR7 expression was examined in 83 human GC tissues and adjacent non-cancer tissues (ANCTs) by immunohistochemistry, in three human GC cell lines (MGC-803, BGC-823 and SGC-7901) by reverse transcription-PCR and western blot. CXCR7 was stably knocked down via lentiviral vectors. The cells proliferation was evaluated using CCK-8 and colony formation assay; MAPK pathways (ERK1/2, p38 and SAPK/JNK) were detected using western blot. Besides, the xenograft model of nude mice for GC growth was performed.

RESULTS: CXCR7 expression in GC tissues was significantly higher than that in ANCTs and associated with tumor size, TNM stage and lymph node metastasis. CXCR7 and CXCR4 were both detectable in three GC cell lines and SGC-7901 cells expressed CXCR7 the most abundantly. SDF-1 promoted the proliferation of SGC-7901 cells, the phosphorylation of ERK1/2, p38 and CXCR7 knockdown distinctly reversed these changes; the proliferation stimulated with SDF-1 was attenuated by U0126 (MEK1/2 inhibitor). Furthermore, CXCR7 knockdown inhibited the growth of GC subcutaneous xenografts and decreased the microvessel density and VEGF expression in vivo.

CONCLUSION: CXCR7 was identified as a novel promoter in GC initiation and progression.