Effect of matrix metalloproteinase-26 on human glioma angiogenesis
10.13315/j.cnki.cjcep.2017.06.007
- VernacularTitle:基质金属蛋白酶-26在人脑胶质瘤血管新生中的作用
- Author:
Yuhui ZHANG
;
Wei LI
;
Xiangxiang LI
;
Bo FANG
;
Xiaona CHANG
;
Chenchen TANG
;
Lihong ZHANG
;
Yilei LI
- Keywords:
brain neoplasms;
human brain glioma;
MMP-26;
VEGF;
angiogenesis
- From:
Chinese Journal of Clinical and Experimental Pathology
2017;33(6):623-628
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the effect of MMP-26 on human glioma angiogenesis and the possible mechanism.Methods The MMP-26 plasmid and empty plasmid pcDNA3.1 were stably transfected into U251 cells to establish a nude mice xenograft model,and then an in vitro human tumor tissue-based three-dimensional angiagenic model.Tissue disks were visually assessed over time to determine the percentage of wells that developed an angiogenic response(I%) and the density and length of neovessel growth were graded at intervals using a semiquantitative visual growth-rating scheme (angiogenic index,AI,0-16scale) in groups of MMP-26 transfected U251 cells (U251-MMP-26),pcDNA3.1 vector-transfected U251 cells (U251-pcDNA3.1) and non-transfected U251 cells (U251).RT-PCR and immunohistochemistry were used to detect the expression of mRNA and protein of MMP-26 and VEGF in groups of U251-MMP-26,U251-pcDNA3.1 and U251.Immunohistochemical localization of CD31 was determined in the endothelial tubes invading the fibrin-thrombin clot matrix.Results Immunohistochemical endothelial cell markers CD31 was positive in the vascular tubes invading the fibrin-thrombin clot matrix,confirming their endothelial origin.The angiogenesis results showed that difference of length of micro capillaries,density of branches,and the area occupied between U251-MMP-26 groups and control groups were significant.The percentage of tumor implants that developed invasion (I%) and the angiogenic index AI in U251-MMP-26 group on day 14 were higher than those of U251-pcDNA3.1 group and U251 group (P < 0.05).The trends of I% and AI in 14 days were significant compared with those in control groups.The expression of mRNA and protein of MMP-26and VEGF in U251-MMP-26 group was significantly higher in U251-MMP-26 group than those in U251-pcDNA3.1 group and U251 group(P <0.01).Conclusion The effect of MMP-26 on promoting glioma angiogenesis may be related to the increased expression of VEGF,which can be used as targets for anti-tumor therapy.