title: Glycoprotein non-metastaticmelanoma protein B promotes glioma motility and angiogenesis through the Wnt/β-catenin signaling pathway.
abstract: Glioma is a common tumor with high mortality and poor overall survival. However, the regulatory mechanisms of glioma tumorigenesis and glioma cell motility are completely unknown. Here, we investigated the role of glycoprotein non-metastatic melanoma protein B in glioma. The expression of glycoprotein non-metastatic melanoma protein B is observed to be aberrantly regulated in glioma tissues and cells, and high levels of glycoprotein non-metastatic melanoma protein B present an inverse correlation with the survival of glioma patients. Compared with the control, glycoprotein non-metastatic melanoma protein B inhibition significantly retarded the proliferation and migration of human glioma cells. The tube formation ability of HBMECs induced by glioma cells was also remarkably reduced by glycoprotein non-metastatic melanoma protein B silencing. Increased levels of VEGF-C and TEM7 were down-regulated by the suppression of glycoprotein non-metastatic melanoma protein B in glioma cells. Additionally, the activity of MMP-2/3/9 was assessed in glioma cells using Western blotting and gelatin zymography assay; their activities were strongly decreased following the suppression of glycoprotein non-metastatic melanoma protein B. Further studies suggested that canonical Wnt/β-catenin pathway was activated, but was inactivated by glycoprotein non-metastatic melanoma protein B suppression in glioma cells. In conclusion, we demonstrate that glycoprotein non-metastatic melanoma protein B might be an inducer for glioma and could enhance matrix metalloproteinase activity through Wnt/β-catenin pathway to contribute to glioma tumorigenesis. This may represent a new understanding for malignant glioma.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China baogangxa@sina.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Ruichun
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Xu
authors.affiliation: Centre for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Baixiang
authors.initials: B
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C503042:GPNMB protein, human; D008562:Membrane Glycoproteins; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Glioma; Wnt/β-catenin pathway; angiogenesis; glycoprotein non-metastatic melanoma protein B; matrix metalloproteinases; tumorigenesis