VE-statin/Egfl7 expression in malignant glioma and its relevant molecular network.

Abstract

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.

• Authors: Chunhai Huang, Xianrui Yuan, Yi Wan, Fei Liu, Xiaoyu Chen, Xianquan Zhan, Xuejun Li
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 7 Issue 3 Pg. 1022-31 ( 2014) ISSN: 1936-2625 [Electronic] United States
• PMID: 24696719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• EGF Family of Proteins
• EGFL7 protein, human
• Endothelial Growth Factors

Topics

• Adult
• Brain Neoplasms (metabolism, pathology)
• Calcium-Binding Proteins
• EGF Family of Proteins
• Endothelial Cells (metabolism)
• Endothelial Growth Factors (biosynthesis)
• Female
• Glioma (metabolism, pathology)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Neovascularization, Pathologic (metabolism)
• Oligonucleotide Array Sequence Analysis
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (physiology)