AIM To research the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. 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) 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 gene suppressed these procedures. CXCR7 was regarded as a potential restorative target for the treating gastric cancer. Intro Gastric carcinoma can be an illness with a higher death rate, rendering it the next most common reason behind cancer death world-wide, following lung tumor. The high mortality of gastric tumor is because of metastasis, and the most frequent metastatic site may be the lymph nodes, accompanied by the liver organ, indicating an immediate dependence on fresh diagnostic treatment and markers techniques[1,2]. Lately, chemokines and their receptors have already been found to become expressed on tumor cells and could mediate cancer development and metastasis. Malignant cells can communicate chemokine receptors and react to chemokine gradients, which might be linked to the spread and growth of cancer. Stromal cell-derived element 1 (SDF-1) can be an essential chemotactic element that stimulates proliferation, dissociation, migration, and invasion in a multitude of tumor cells, including gastric tumor[3-5]. For quite some time, CXCR4 was thought to be the just receptor for CXCL12. Nevertheless, several recent reviews have provided proof that CXCR7 (RDC-1) can be an determined chemokine receptor that stocks the same ligand (CXCL12) as CXCR4. CXCL12 binds to CXCR7 with higher affinity than CXCR4 (Kd = 0.4 nmol/L 3.6 nmol/L)[2]. In human beings, CXCR7 can be indicated in embryonic center and neuronal cells, some hematopoietic cells, and triggered endothelium[6,7], but on few additional regular cell types. Furthermore, CXCR7 is indicated in various malignancies, including breast cancers[8], lung tumor[9], and glioma[10], and was shown to promote the growth and metastasis of various tumor models[9,10]. The main ligand for CXCR7 is usually CXCL12, which binds to CXCR7 with high affinity, but CXCR7 may also bind the alternative ligand CXCL11 with low affinity. Although CXCR7 is usually expressed by many different tumors, studies of CXCR7 expression in gastric cancer are few in number. Zhi et al[11] and Ma Ertapenem sodium 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 at the time of gastrectomy (confirmed by either histopathological examination or Rabbit Polyclonal to OR5B3 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 signed up for the scholarly research hadn’t received any chemo- or radiotherapy Ertapenem sodium before medical diagnosis. Routine chemotherapy had received to the sufferers with an advanced-stage disease after procedure, Ertapenem sodium but no rays treatment was performed in virtually any of sufferers contained in our research. Sufferers had been excluded if indeed they got been subjected to any targeted therapy previously, chemotherapy, radiotherapy, or involvement therapy for gastric tumor. Reagents The individual recombinant CXCL12 as well as the mouse Ertapenem sodium anti-human CXCR7 monoclonal antibody had been extracted from Dako Business. CXCR7-particular siRNA and CXCR7 overexpressing vector had been bought from Santa Cruz Biotechnology (Santa Cruz, CA, USA). The CCK-8 reagent package was bought from Sigma (USA). Total RNA removal kits (RNAfast200) had been bought from Fastagen Biotechnology (Shanghai); slow transcription kits had been bought from TaKaRa (Japan). PCR primers had been synthesized by Shanghai Bioengineering & Technology Providers. Millicell little chambers had been bought from Millipore (USA); MTS and Matrigel products were purchased.