Downregulation of programmed cell death 10 is associated with tumor cell proliferation, hyperangiogenesis and peritumoral edema in human glioblastoma

BMC Cancer

Research Article

Oliver Mueller¹  Nicolai El Hindy¹  Philipp Dammann¹  Ulrich Sure¹  Nicole Lambertz¹  Yuan Zhu¹  Ilonka Kreitschmann-Andermahr¹  Neriman Oezkan¹  Klaus Peter Stein² 

[1] Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany;Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany;Present Address: Department of Neurosurgery, KRH Klinikum Nordstadt, Haltenhoffstr. 41, 30167, Hannover, Germany;

关键词: Primary glioblastoma;    PDCD10/CCM3;    Tumor cell proliferation;    Tumor cell apoptosis;    Microvessel density;    Angiogenesis;    Peritumoral edema;   

DOI  :  10.1186/s12885-015-1709-8

 received in 2015-01-12, accepted in 2015-10-08,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundNeovascularization and peritumoral edema are hallmarks of glioblastoma (GBM). Programmed cell death 10 (PDCD10) plays a pivotal role in regulating apoptosis, neoangiogenesis and vessel permeability and is implicated in certain tumor signaling pathways. However, little is known about PDCD10 in GBM. We aimed to investigate the expression pattern of PDCD10 and to identify the association of its expression with some molecular and clinical parameters in human GBM.MethodsmRNA and protein expression of PDCD10 were examined respectively by real-time RT-PCR and Western blotting in GBM (n = 27), astrocytoma grade II (n = 13) and control (n = 11). The protein level of p-Akt and GFAP was detected by Western blot. Double-imunofluorecent staining was performed to reveal the cellular expression profile of PDCD10. Brain edema and microvascular density (MVD) were respectively analyzed based on pre-operative MRI and after laminin immnostaining. MGMT promoter methylation was detected by methylation specific PCR.ResultsmRNA and protein levels of PDCD10 were significantly downregulated in GBM, concomitantly accompanied by the activation of Akt. PDCD10 immunoreactivity was absent in proliferating tumor cells, endothelial cells and GFAP-positive cells, but exclusively present in the hypoxic pseudopalisading cells which underwent apoptosis. Moreover, loss of PDCD10 was associated with a higher MVD and a more severe peritumoral edema but not with MGMT promoter methylation in GBM.ConclusionWe report for the first time that PDCD10 expression is downregulated in GBM, which is associated with the activation of Akt signaling protein. PDCD10 is potentially implicated in tumor proliferation and apoptosis, hyperangiogenesis and peritumoral edema in GBM.

【 授权许可】

CC BY   
© Lambertz et al. 2015