BackgroundNeuropilin-1 (NRP-1) is a transmembrane glycoprotein participating in the growth and metastasis of cancer cells as multifunctional co-receptors by interacting with the signaling pathways. However, its role in gastric cancer has not yet been clarified. This study aims to investigate whether NRP-1 expression is associated with the clinicopathology of gastric cancer, and involved in the growth and metastasis of gastric cancer cells.MethodsNRP-1 expression in clinical gastric cancer specimens was examined by immunohistochemistry and its association with clinicopathology analyzed. The expression of NRP-1 in a panel of human gastric cancer cells was examined by real-time RT-PCR and immunoblotting. Stable transfectants depleted of NRP-1, termed MGC-803-NRPlow, were generated from MGC-803 cells. Cell proliferation was analyzed by the Cell Counting Kit-8 and Bromodeoxyuridine incorporation assays, and migrating ability analyzed by migration assays. The xenograft model was used to assess the effects of NRP-1 depletion on tumorigenesis, growth, metastasis and therapeutic potentials. The role of NRP-1 as co-receptors in the signaling pathways stimulated by ligands was examined. The key molecules involved in cell proliferation, migration and related signaling pathways were detected by immunoblotting.ResultsGastric cancer tissues expressed higher levels of NRP-1 compared to normal gastric mucosa. Its expression correlated with clinical staging, tumor differentiation and pathological types. NRP-1 depletion inhibited cell proliferation by inducing cell cycle arrest in the G1/S phase by upregulating p27, and downregulating cyclin E and cyclin-dependent kinase 2. NRP-1 depletion reduced the ability of cells to migrate by inhibiting the phosphorylation of focal adhesion kinase. NRP-1 depletion suppressed tumorigenesis, tumor growth and lung metastasis by inhibiting cell proliferation and tumor angiogenesis in situ. Therapeutic NRP-1 shRNA inhibited the growth of established BGC823 tumors. Depletion of NRP-1 inhibited the activation of VEGF/VEGFR2, EGF/EGFR and HGF/c-Met pathways stimulated by respective recombinant human VEGF-165, EGF and HGF proteins.ConclusionsThe present results indicate that NRP-1 may be a potentially valuable biomarker and therapeutic target for gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0291-5) contains supplementary material, which is available to authorized users.
The biomaterials used for central nervous system injury require not only interacting with specific cell adhesion but also specific growth factor receptors to promote nerve regeneration. In this study, hyaluronic acid (HA)-based hydrogels modified with poly-L-lysine (PLL) and nogo-66 receptor antibody (antiNgR) (HA-PLL/antiNgR) were administered to rats after lateral hemisection of the spinal cord. Anti-neurofilament positive axons were found to extend into the HA-PLL/antiNgR hydrogel at 8 weeks after implantation, which shows significant difference compared with HA-PLL or blank control group. Electron micrographs of implanted hydrogels showed that there were more cells and normal axons with myelin in the HA-PLL/antiNgR implant than that of HA-PLL hydrogel. The antiNgR grafted on HA hydrogels could be detected for 8 weeks after transplantation in vivo. All of these properties may facilitate HA-PLL/antiNgR hydrogels to become a promising scaffold for repairing spinal cord injury. Nevertheless, both two kinds of modified hydrogels (HA-PLL/antiNgR and HA-PLL) showed remarkable advantages in supporting angiogenesis, and simultaneously inhibiting the formation of glial scar.
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