title: Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion.
abstract: Glioblastoma (GBM) is the most prevalent malignant primary brain tumor in adults and exhibits a spectrum of aberrantly aggressive phenotype. Tumor cell proliferation and invasion are critically regulated by chemokines and their receptors. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. Nonetheless, the roles of the CCR5 in GBM still remain unclear. The present study provides the evidence that the chemokine receptor CCR5 is highly expressed and associated with poor prognosis in human GBM. Mechanistically, CCL5-CCR5 mediates activation of Akt, and subsequently induces proliferation and invasive responses in U87 and U251 cells. Moreover, down-regulation of CCR5 significantly inhibited the growth of glioma in U87 tumor xenograft mouse model. Finally, high CCR5 expression in GBM is correlated with increased p-Akt expression in patient samples. Together, these findings suggest that the CCR5 is a critical molecular event associated with gliomagenesis.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Lanfu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China smhe123@163.com.
authors.forename: Shiming
authors.initials: S
authors.lastname: He
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D064593:Heterografts; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D019713:Receptors, CCR5 / Q000378:metabolism*
chemical_list: C584933:CCR5 protein, human; D018946:Chemokine CCL5; D019713:Receptors, CCR5
keywords: Akt pathway; CCR5; carcinogenesis; glioblastoma; invasion