Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (= 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (= 0.338, = 0.000) Pax1 and liver metastasis (= 0.629, = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (= 0.010; = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (= 0.338, = 0.000; = 0.629, = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer. gene promoted cell proliferation, migration and invasion. Silencing of the LY-2584702 hydrochloride gene suppressed these processes. CXCR7 was considered a potential therapeutic target for the treatment of gastric cancer. INTRODUCTION Gastric carcinoma is a disease with a high death rate, making it the second most common cause of cancer death worldwide, following lung cancer. The high mortality of gastric cancer is due to metastasis, and the most common metastatic site is the lymph nodes, followed by the liver, indicating an urgent need for new diagnostic markers and treatment approaches[1,2]. In recent years, chemokines and their receptors have been found to be expressed on cancer cells and may mediate cancer progression and metastasis. Malignant cells can express chemokine receptors and respond to chemokine gradients, which may be related to the growth and spread of cancer. Stromal cell-derived factor 1 (SDF-1) is a very important chemotactic factor that stimulates proliferation, dissociation, migration, and invasion in a wide variety of tumor cells, including gastric cancer[3-5]. For many years, CXCR4 was believed to be the only receptor for CXCL12. However, several recent reports have provided evidence that CXCR7 (RDC-1) is an identified chemokine receptor that shares the same ligand (CXCL12) as CXCR4. CXCL12 binds to CXCR7 with greater affinity than CXCR4 (Kd = 0.4 nmol/L 3.6 nmol/L)[2]. In humans, CXCR7 is expressed in embryonic neuronal and heart tissue, some hematopoietic cells, and activated endothelium[6,7], but on few other normal cell types. Moreover, CXCR7 is expressed in various cancers, including breast cancer[8], lung cancer[9], and glioma[10], and was shown to promote the growth and metastasis of various tumor models[9,10]. The main ligand for CXCR7 LY-2584702 hydrochloride is CXCL12, which binds to CXCR7 with high affinity, but CXCR7 may also bind the alternative ligand CXCL11 with low affinity. Although CXCR7 is expressed by many different tumors, studies of CXCR7 expression in gastric cancer are few in number. Zhi et al[11] and Ma et al[12] have reported that CXCR7 transcripts have been detected in gastric cancer cells, including MGC803, SGC7901 and BGC823 cells, and Lee et al[5] reported that CXCR7 was differentially expressed in gastric adenocarcinoma tissues. However, most of the studies concerning CXCL12 and CXCR7 have been conducted = 66) and pT3 + pT4 (= 94), with positive nodal involvement in 96 cases (all confirmed by histopathological examination) and 30 cases having liver metastasis LY-2584702 hydrochloride at the time of gastrectomy (confirmed by either histopathological examination or computed tomography). The lymph nodes around the stomach did not have metastasis in 64 cases. Twenty-nine liver tissues with no metastasis came from resected specimens of non-neoplastic diseases, and 29 liver metastasis tissues were from patients with intestinal-type gastric cancer (after the imaging diagnosis of liver metastasis of gastric cancer, one of the 30 patients refused to undergo fine-needle aspiration). Patients enrolled in the study had not received any chemo- or radiotherapy before diagnosis. Routine chemotherapy had been given to the patients with an advanced-stage disease after operation, but no radiation treatment was performed in any of patients included in our study. Patients were excluded if they had previously been exposed to any targeted therapy, chemotherapy, radiotherapy, or intervention therapy for gastric cancer. Reagents The human recombinant CXCL12 and the mouse anti-human CXCR7 monoclonal antibody were obtained from Dako Company. CXCR7-specific siRNA and CXCR7 overexpressing vector were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, United States). The CCK-8 reagent kit was purchased from Sigma (United States). Total RNA extraction kits (RNAfast200) were purchased from Fastagen Biotechnology (Shanghai); reverse transcription kits were purchased from TaKaRa (Japan). PCR primers were synthesized by Shanghai Bioengineering & Technology Services. Millicell small chambers were purchased from Millipore.