Abstract
BackgroundMore recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of gastric cancer cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in gastric cancer cell lines and to evaluate the role of CXCR7 in the proliferation, invasion, adhesion, and angiogenesis of gastric cancer cells.MethodsReal-time PCR and Western blotting were used to examine the mRNA and protein levels of CXCR4 and CXCR7 in five gastric cancer cell lines (HGC-27, MGC-803, BGC-823, SGC-7901, and MKN-28). CXCR7-expressing shRNA was constructed and subsequently stably transfected into the human gastric cancer cells. In addition, the effect of CXCR7 inhibition on cell proliferation, invasion, adhesion, VEGF secretion, and tube formation was evaluated.ResultsThe mRNA and protein of CXCR7 were expressed in all five gastric cancer cell lines; in particular, the expression of CXCR7 was the highest in SGC-7901 cells. Stromal cell-derived factor-1 (SDF-1) was found to induce proliferation, invasion, adhesion, and tube formation. Moreover, the VEGF secretion in SGC-7901 cells was also enhanced by SDF-1 stimulation. These biological effects were inhibited by the silencing of CXCR7 in SGC-7901 cells.ConclusionsIncreased CXCR7 expression was found in gastric cancer cells. Knockdown of CXCR7 expression by transfection with CXCR7shRNA significantly inhibits SGC-7901 cells’ proliferation, invasion, adhesion, and angiogenesis. This study provides new insights into the significance of CXCR7 in the invasion and angiogenesis of gastric cancer.
Highlights
More recent studies have revealed that chemokine receptor CXC chemokine receptor type 7 (CXCR7) plays an important role in cancer development
Expression of CXCR7 on gastric cancer cell lines and human umbilical vein endothelial cells (HUVECs) To determine whether CXCR7 is expressed in gastric cancer cell lines, we first evaluated the expression of CXCR7 by Western blot in a panel of gastric cancer cell lines (HGC-27, MGC-803, BGC-823, SGC-7901, and MKN-28) and HUVEC
Interaction between CXCR7 and Stromal cell-derived factor-1 (SDF-1) in SGC-7901 cells In order to prove the interaction between CXCR7 and SDF-1 in SGC-7901 cells, the total protein extracts from SGC-7901 cells were immunoprecipitated with an anti-CXCR7 or anti-SDF-1 antibody, precipitated proteins were analyzed by immunoblotting with antibodies directed to either CXCR7 or SDF-1
Summary
More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. Little is known about the effect of CXCR7 on the process of gastric cancer cell invasion and angiogenesis. Stromal cell-derived factor-1 (SDF-1, called CXCL12) is a member of the CXC subfamily of chemokines and is expressed in a variety of tissues including the lung, liver, bone marrow, and lymph nodes [3,4,5]. SDF-1 plays a role in a number of important physiological processes including leukocyte trafficking and vasculogenesis [7, 8]. SDF-1 plays a crucial role in the process of invasion and metastasis of tumor cells [9]. SDF-1 stimulates proliferation, dissociation, migration, and invasion in a wide variety of tumor cells, including breast cancer cells [10], pancreatic cancer cells [11] and HCC cells [12], and gastric cancer cells [13]
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