title: Glutamine synthetase functions as a negative growth regulator in glioma.
abstract: Our recent study demonstrated that glutamine synthetase (GS) may not only serve as a glutamate-converting enzyme in glial cells, but may also function as a regulator of astrocyte migration after injury. In this report, we showed that GS expression increased in cultured rat C6 glioma cells that underwent long-term serially propagation. The stable overexpression of GS in C6 glioma cells resulted in growth arrest and motility suppression; however the stable knockdown of GS resulted in motility enhancement. In correlation with cell aggregation, N-cadherin levels increased at sites of cell-cell contact in C6 cells overexpressing GS, and decreased in C6 cells with stable GS knockdown; total N-cadherin expression levels remained unchanged in these cells. In addition, levels of p21, a potent cyclin-dependent kinase inhibitor, increased, while cyclin D1 levels decreased in C6 cells overexpressing GS. Our additional studies showed that N-cadherin-mediated cell-cell contacts were implicated in GS-induced cell growth arrest and impairment of cell migration, as evidenced by the inhibition of GS on cell growth and motility by the neutralizing anti-N-cadherin monoclonal antibody (GC-4 mAb). Collectively, these observations suggest a novel mechanism of growth regulation by GS that involves N-cadherin mediated cell-cell contact.
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, 214023, Jiangsu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Weifeng
authors.initials: W
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Deng
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Weizhen
authors.initials: W
authors.lastname: Qiao
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.forename: Chunxing
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005973:Glutamine / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D005973:Glutamine; D049452:Green Fluorescent Proteins; D005974:Glutamate-Ammonia Ligase