标题:Interplay of VEGFa and MMP2 regulates invasion of glioblastoma
作者:Gong, Jie;Zhu, Shugan;Zhang, Yuan;Wang, Jiangang
作者机构:Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan 250012, Shandong, Peoples R China;Shandong Univ, Qilu Hosp, Dept Neurosurg, Jina
通讯作者:Zhang, Y
通讯作者地址:[Zhang, Y]Shandong Univ, Qilu Hosp, Dept Neurosurg, 107 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China.
来源:Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine
出版年:2014
卷:35
期:12
页码:11879-11885
DOI:10.1007/s13277-014-2438-3
关键词:Glioblastoma;Vascular endothelial growth factor a;Matrix metalloproteinases 2;ERK/MAPK;Invasion
摘要:Neovascularization plays a substantial role in the regulation of invasion of glioblastoma. However, the under-lying-molecular basis remains largely unknown. Both vascular endothelial growth factor a (VEGFa) and matrix metalloproteinases 2 (MMP2) are essential for cancer neovascularization and cancer invasion in that they promote endothelial mitogenesis and permeability, and promote extracellular matrix degradation, respectively. In the current study, we found strong positive correlation of VEGFa and phosphorylated MMP2 levels in the glioblastoma from the patients. Thus, we used a human glioblastoma line, A-172, to examine the interaction of VEGFa and MMP2. We found that overexpression of VEGFa in A-172 cells increased MMP2 levels, while inhibition of VEGFa in A-172 cells decreased MMP2 levels. On the other hand, forced changes in MMP2 levels in A-172 cells did not affect VEGFa levels. These data suggest that VEGFa may regulate MMP2 in glioblastoma, while MMP2 did not appear to affect VEGFa levels. We then examined the signaling pathways involved in the regulation of MMP2 levels by VEGFa. Application of a specific extracellular-related kinase 1/2 (ERK1/2) inhibitor, but not application of either an protein kinase B (Akt) inhibitor, or a Jun N-terminal kinase (JNK) inhibitor to VEGFa-overexpressing A-172 cells substantially abolished the effect of VEGFa on MMP2 activation, suggesting that VEGFa may increase MMP2 levels via ERK/mitogen-activated protein kinase (MAPK), but not phosphatidylinositol 3-kinase (PI3K) or JNK signaling pathways in glioblastoma. Moreover, adapted VEGFa levels were found to directly and positively affect the glioblastoma development in an intracranial glioblastoma implantation model. Taken together, our data suggest that anti-VEGFa treatment in glioblastoma may inhibit neovascularization not only by VEGFa itself but also by its regulatory effect on MMP2.
收录类别:SCIE
WOS核心被引频次:23
资源类型:期刊论文
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