PMID- 25175735 OWN - NLM STAT- MEDLINE DCOM- 20151026 LR - 20211203 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 32 IP - 5 DP - 2014 Nov TI - Mammalian target of rapamycin signaling is involved in the vasculogenic mimicry of glioma via hypoxia-inducible factor-1alpha. PG - 1973-80 LID - 10.3892/or.2014.3454 [doi] AB - 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-1alpha. Taken together, our results demonstrated that mTOR signaling is involved in VM formation, and may be a potential therapeutic target for gliomas. FAU - Huang, Min AU - Huang M AD - 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. FAU - Ke, Yiquan AU - Ke Y AD - 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. FAU - Sun, Xinlin AU - Sun X AD - 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. FAU - Yu, Li AU - Yu L AD - Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China. FAU - Yang, Zhilin AU - Yang Z AD - 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. FAU - Zhang, Yonghong AU - Zhang Y AD - 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. FAU - Du, Mouxuan AU - Du M AD - 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. FAU - Wang, Jihui AU - Wang J AD - 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. FAU - Liu, Xiao AU - Liu X AD - 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. FAU - Huang, Shuyun AU - Huang S AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140829 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cell Hypoxia/drug effects MH - Cell Line, Tumor MH - Female MH - Glioma/*blood supply/metabolism/*pathology MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - In Vitro Techniques MH - Male MH - Middle Aged MH - Neovascularization, Pathologic/metabolism/*pathology MH - *Signal Transduction/drug effects MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/*metabolism EDAT- 2014/09/02 06:00 MHDA- 2015/10/27 06:00 CRDT- 2014/09/02 06:00 PHST- 2014/07/11 00:00 [received] PHST- 2014/08/14 00:00 [accepted] PHST- 2014/09/02 06:00 [entrez] PHST- 2014/09/02 06:00 [pubmed] PHST- 2015/10/27 06:00 [medline] AID - 10.3892/or.2014.3454 [doi] PST - ppublish SO - Oncol Rep. 2014 Nov;32(5):1973-80. doi: 10.3892/or.2014.3454. Epub 2014 Aug 29.