A MT1-MMP/NF-kappaB signaling axis as a checkpoint controller of COX-2 expression in CD133+ U87 glioblastoma cells.
A MT1-MMP/NF-kappaB signaling axis as a checkpoint controller of COX-2 expression in CD133+ U87 glioblastoma cells.
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DOI：
10.1186/1742-2094-6-8
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发表时间：
2009-03-09
影响因子：
9.3
通讯作者：
Béliveau R
中科院分区：
文献类型：
--
作者：
Annabi B;Laflamme C;Sina A;Lachambre MP;Béliveau R
复发性胶质瘤中的CD 133（+）干细胞群与临床特征相关，如治疗抵抗、血脑屏障破坏以及肿瘤浸润。对一组组织学分级增高的胶质瘤样本进行筛选，发现CD 133（+）细胞的频率与环氧合酶（考克斯）-2和1型基质金属蛋白酶（MT 1-MMP）的高表达相关。我们使用qRT-PCR和免疫印迹检测MT 1-MMP和考克斯-2基因和蛋白表达在亲本、CD 133（+）和神经球U87胶质瘤细胞培养物中的分子相互作用。我们发现，CD 133，考克斯-2和MT 1-MMP的表达增强时，胶质瘤细胞培养在神经球条件。用磁性细胞分选技术从亲本U87细胞中分离的CD 133（+）富集的U87胶质瘤细胞群也生长为神经球，并显示增强的考克斯-2表达。MT 1-MMP基因沉默可抑制考克斯-2在神经球中的表达，而重组MT 1-MMP的过表达可直接触发U87细胞中考克斯-2的表达，而不依赖于MT 1-MMP的催化功能。MT 1-MMP对考克斯-2的诱导作用在野生型和NF-κB B p65-/-突变小鼠胚胎成纤维细胞中也得到了验证，但在NF-κB1（p50-/-）突变细胞中被废除。我们提供了CD 133（+）胶质瘤细胞中考克斯-2表达增强的证据，并直接提供了NF-κ B介导的考克斯-2通过MT 1-MMP调节的细胞基础证据。这种检查点控制的生物学意义可以解释负责癌症干细胞的治疗抗性表型的炎症平衡的考克斯-2依赖性机制。
The CD133(+) stem cell population in recurrent gliomas is associated with clinical features such as therapy resistance, blood-brain barrier disruption and, hence, tumor infiltration. Screening of a large panel of glioma samples increasing histological grade demonstrated frequencies of CD133(+) cells which correlated with high expression of cyclooxygenase (COX)-2 and of membrane type-1 matrix metalloproteinase (MT1-MMP). We used qRT-PCR and immunoblotting to examine the molecular interplay between MT1-MMP and COX-2 gene and protein expression in parental, CD133(+), and neurospheres U87 glioma cell cultures. We found that CD133, COX-2 and MT1-MMP expression were enhanced when glioma cells were cultured in neurosphere conditions. A CD133(+)-enriched U87 glioma cell population, isolated from parental U87 cells with magnetic cell sorting technology, also grew as neurospheres and showed enhanced COX-2 expression. MT1-MMP gene silencing antagonized COX-2 expression in neurospheres, while overexpression of recombinant MT1-MMP directly triggered COX-2 expression in U87 cells independent from MT1-MMP's catalytic function. COX-2 induction by MT1-MMP was also validated in wild-type and in NF-κB p65-/- mutant mouse embryonic fibroblasts, but was abrogated in NF-κB1 (p50-/-) mutant cells. We provide evidence for enhanced COX-2 expression in CD133(+) glioma cells, and direct cell-based evidence of NF-κB-mediated COX-2 regulation by MT1-MMP. The biological significance of such checkpoint control may account for COX-2-dependent mechanisms of inflammatory balance responsible of therapy resistance phenotype of cancer stem cells.
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DOI：
10.1016/0090-6980(87)90052-9
发表时间：
1987-01-01
期刊：
PROSTAGLANDINS
影响因子：
--
作者：
HANSON, WR;DELAURENTIIS, K
通讯作者：
DELAURENTIIS, K
影响因子：
3.3
作者：
Korkolopoulou, Penelope;Levidou, Georgia;Patsouris, Efstratios
通讯作者：
Patsouris, Efstratios
影响因子：
3.9
作者：
Bijnsdorp, Irene V.;van den Berg, Jaap;Sminia, Peter
通讯作者：
Sminia, Peter
影响因子：
12.7
作者：
Deininger, MH;Weller, M;Meyermann, R
通讯作者：
Meyermann, R
影响因子：
3.5
作者：
Fortier, Simon;Labelle, Dominique;Annabi, Borhane
通讯作者：
Annabi, Borhane