title: HGF/MET signaling promotes glioma growth via up-regulation of Cox-2 expression and PGE2 production.
abstract: Cyclooxygenase2 (Cox-2) is well known for glioma growth through up-regulation of prostaglandin E2 (PGE2) levels. MET, a hepatocyte growth factor (HGF) receptor, is also frequently high expressed in glioma, which promotes glioma growth and invasion. Here, we demonstrate that HGF/MET signaling can promote PGE2 production in glioma cells via Cox-2 up-regulation. RNA inhibition of MET suggested that MET signaling is essential for Cox-2 up-regulation. Moreover, HGF could enhance Cox-2 expression and PGE2 release. Knockdown of Cox-2 inhibited growth-promoting effects of HGF, suggesting that HGF/MET functioned via Cox-2/PGE2 pathway. Therefore, our work reveals a critical relationship of Cox-2/PGE2 and HGF/MET signaling in promoting glioma cells proliferation. Further, targeting MET and Cox-2 may represent an attractive target therapy for glioma.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternal and Children's Hospital, Shanghai Jiaotong University Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Wenzong
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Junhe
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China ; Department of Neurosurgery, Huashan Hospital, Fudan University Shanghai 200040, China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150086, China.
authors.forename: Chuanlu
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D015232:Dinoprostone
keywords: Cox-2; GBMs; MET; PGE2