title: Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1α.
abstract: The mammalian target of rapamycin (mTOR) is a crucial regulator in malignant gliomas. Vasculogenic mimicry (VM) describes functional channels established by highly malignant tumor cells that is different from endothelium-lined blood vessels. Our previous studies confirmed the existence and clinical significance of VM in medulloblastoma and glioblastoma. In the present study, by immunohistochemical and CD34/PAS histochemical double-staining, 34 cases (26.8%) with VM structures were identified among a total of 127 glioma cases, and these VM structures were associated with mTOR expression in the glioma specimens. In vitro, U87 malignant glioblastoma cells formed tube structures similar to HUVECs on Matrigel in 3D culture, and mTOR-specific inhibitor rapamycin inhibited VM formation in the U87 malignant glioblastoma cells under both normoxia and hypoxia. In addition, rapamycin and mTOR siRNA inhibited molecules in the signaling cascade of VM formation, particularly HIF-1α. Taken together, our results demonstrated that mTOR signaling is involved in VM formation, and may be a potential therapeutic target for gliomas.
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Yiquan
authors.initials: Y
authors.lastname: Ke
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Mouxuan
authors.initials: M
authors.lastname: Du
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Wang
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D005910:Glioma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus