title: Role of Protease-Activated Receptor-1 in Glioma Growth.
abstract: Activation of a thrombin receptor, protease-activated receptor-1 (PAR-1), induces angiogenesis, cell proliferation, and invasion in tumors. The present study examined the effect of host PAR-1 gene deletion on glioma growth in a mouse model. F98 glioma cells were implanted into the right caudate of either wild type (WT) or PAR-1 knockout (KO) mice. Mice underwent magnetic resonance imaging (MRI) and the brains were used for measurements of brain water content and tumor mass. Levels of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were also measured by ELISA (enzyme-linked immunosorbent assay). We found brain water content in the ipsilateral hemisphere and the tumor mass were significantly lower in PAR-1 KO than WT mice at day 12 after implantation of F98 cells (p < 0.05). HIF-1α protein levels in the ipsilateral hemisphere were higher in the WT mice (373 ± 25 pg/g brain tissue vs 333 ± 35 pg/g brain tissue in PAR-1 KO mice, p < 0.05) 7 days after F98 cell implantation. VEGF protein levels were also higher in the ipsilateral hemisphere of WT mice (219 ± 21 vs 166 ± 22 pg/g brain tissue in PAR-1 KO mice, p < 0.01). In conclusion, PAR-1 has a role in glioma growth and could be a new therapeutic target for gliomas.
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.|Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China.
authors.forename: Zhan Hong
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Muraszko
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, University of Michigan, 5018 BSRB, Ann Arbor, MI, 48109-2200, USA. yahua@umich.edu.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D051381:Rats; D044463:Receptor, PAR-1 / Q000235:genetics*; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044463:Receptor, PAR-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: Gliomas; Mouse; Protease-activated receptor−1; Thrombin