title: Upregulation of chemokine receptor CCR10 is essential for glioma proliferation, invasion and patient survival.
abstract: Human gliomas are characterized by their invasion of normal brain structures irrespective of their grade of malignancy. Tumor cell invasion share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptor CCR10 is highly expressed in human glioblastoma compared with control brain tissue. In vitro, signaling through CCL27-CCR10 mediates activation of p-Akt, and subsequently induces proliferation and invasive responses. Cell proliferation and invasion promoted by CCL27 were blocked by inhibition of p-Akt or CCR10. In vivo, down-regulation of CCR10 significantly impairs growth of glioma. Clinically, High CCR10 expression in GBM correlated with p-Akt, shorter overall survival and progression-free survival (P < 0.05). Together, these findings suggest that elevated CCR10 is a critical molecular event associated with gliomagenesis.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, International Peace Maternal and Children's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Wenzong
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054447:Receptors, CCR10 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014162:Transfection; D015854:Up-Regulation
chemical_list: C515706:CCR10 protein, human; D054447:Receptors, CCR10; D051057:Proto-Oncogene Proteins c-akt