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


METHODS
mRNA 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.


RESULTS
mRNA 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.


CONCLUSIONS
We 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.
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. nicole.lambertz@uk-essen.de.
Nicole
N
Lambertz
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. nicolai.elhindy@uk-essen.de.
Nicolai
N
El Hindy
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. Ilonka.Kreitschmann@uk-essen.de.
Ilonka
I
Kreitschmann-Andermahr
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. klaus-peter.stein@krh.eu.|Present Address: Department of Neurosurgery, KRH Klinikum Nordstadt, Haltenhoffstr. 41, 30167, Hannover, Germany. klaus-peter.stein@krh.eu.
Klaus Peter
KP
Stein
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. philipp.dammann@uk-essen.de.
Philipp
P
Dammann
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. neriman.oezkan@uk-essen.de.
Neriman
N
Oezkan
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. oliver.mueller@uk-essen.de.
Oliver
O
Mueller
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. ulrich.sure@uk-essen.de.
Ulrich
U
Sure
Department of Neurosurgery, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. yuan.zhu@uk-essen.de.
Yuan
Y
Zhu
D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D001929:Brain Edema / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D055806:Microvessels / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051058:Oncogene Protein v-akt