VE-statin/Egfl7 expression in malignant glioma and its relevant molecular network.
This study investigated VE-statin/Egfl7 expression and its role and regulatory mechanism in malignant glioma progression. Forty-five paraffin-embedded glioma (grade I-II: n=24; grade III-IV: n=21) were examined. VE-statin/Egfl7 protein expression was detected via immunohistochemistry, and its correlation with pathological grade was evaluated. Three-dimensional cell culture was then performed to investigate the influence of VE-statin/Egfl7 on the angiogenesis of umbilical vein endothelial cells. Microarray detection was used to molecularly profile VE-statin/Egfl7 and relevant signaling pathways in malignant glioma (U251 cells). Data showed that VE-statin/Egfl7 protein was mainly expressed in the cytoplasm of cancer and vascular endothelial cells and was significantly related to the degree of malignancy (t=4.399, P<0.01). Additionally, VE-statin/Egfl7 expression was low in certain gray-matter neurons but undetectable in glial cells. VE-statin/Egfl7 gene silencing significantly inhibited angiogenesis in umbilical vein endothelial cells. The following microarray results were observed in VE-statin/Egfl7-silenced U251 cells: 1) EGFR family members showed the highest differential expression, accounting for 5.54% of differentially expressed genes; 2) cell survival-related signaling pathways changed significantly; and 3) the integrin ανβ3 signaling pathway was markedly altered. Thus, malignant glioma cells and glioma vascular endothelial cells highly express VE-statin/Egfl7, which is significantly correlated with the degree of malignancy. Moreover, VE-statin/Egfl7 plays an important role in glioma angiogenesis. Microarray results indicate that VE-statin/Egfl7 may regulate EGFR and integrins to influence the FAK activity of downstream factors, triggering the PI3K/Akt and Ras/MAPK cascades and subsequent malignant glioma development.
Department of Neurosurgery, First Affiliated Hospital of Jishou University Jishou 416000, Hunan, China.
Chunhai
C
Huang
Department of Neurosurgery, Xiangya Hospital, Central South University Changsha 410008, Hunan, China ; The Institute of Skull Base Surgery and Neurooncology at Hunan Changsha 410008, Hunan, China.
Xianrui
X
Yuan
Department of Neurosurgery, First Affiliated Hospital of Jishou University Jishou 416000, Hunan, China.
Yi
Y
Wan
Department of Neurosurgery, Xiangya Hospital, Central South University Changsha 410008, Hunan, China ; The Institute of Skull Base Surgery and Neurooncology at Hunan Changsha 410008, Hunan, China.
Fei
F
Liu
Department of Neurosurgery, Xiangya Hospital, Central South University Changsha 410008, Hunan, China ; The Institute of Skull Base Surgery and Neurooncology at Hunan Changsha 410008, Hunan, China.
Xiaoyu
X
Chen
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University Changsha 410008, Hunan, China.
Xianquan
X
Zhan
Department of Neurosurgery, Xiangya Hospital, Central South University Changsha 410008, Hunan, China ; The Institute of Skull Base Surgery and Neurooncology at Hunan Changsha 410008, Hunan, China.
Xuejun
X
Li
D000328:Adult; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; D042783:Endothelial Cells / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
D002135:Calcium-Binding Proteins; D066255:EGF Family of Proteins; C527877:EGFL7 protein, human; D016228:Endothelial Growth Factors
Epidermal growth factor-like domain 7; angiogenesis; glioma; microarray; pathological grade