title: Glioblastoma microvesicles promote endothelial cell proliferation through Akt/beta-catenin pathway.
abstract: Glioblastoma tumor cells release microvesicles, which contain mRNA, miRNA and angiogenic proteins. These tumor-derived microvesicles transfer genetic information and proteins to normal cells. Previous reports demonstrated that the increased microvesicles in cerebrospinal fluid (CSF) of patients with glioblastoma up-regulate procoagulant activity. The concentration of microvesicles was closely related to thromboembolism incidence and clinical therapeutic effects of glioblastoma patients. However, it is still not clear how CSF microvesicles and what factors affect glioblastoma development. In this study, we collected the plasma and CSF from glioblastoma patients and healthy volunteers. Microvesicles acquired from serum or CSF were added to cultured endothelial cells. And the effects of these microvesicles on endothelial cells were examined. Our results showed that microvesicles from CSF of patients, but not from circulating blood, promoted endothelial cells migration and proliferation in vitro. In addition, the degree of endothelial cell proliferation triggered by microvesicles from CSF was reduced when treated with siRNA targeting Akt/beta-catenin, suggesting that the Akt/beta-catenin pathway is involved in the microvesicle-initiated endothelial cell proliferation. In conclusion, glioblastoma mainly affects microvesicles within CSF without showing significant impact on microvesicles in circulating blood. Microvesicles from the CSF of glioblastoma patients may initiate endothelial cell growth and thus promote cell invasion. This effect may be directly exerted by activated Akt/beta-catenin pathway.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Shihai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Surgical Oncology, Zhejiang University School of Medicine Hangzhou, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Soochow University 1055 Sanxiang Road, Suzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D034741:RNA, Small Interfering; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt/beta-catenin; Microvesicles; endothelial cells; glioblastoma