Sartor Luigi, Negro Alessandro, Barletta Emanuela, Mugnai Gabriele, Garbisa Spiridione
Department of Experimental Biomedical Sciences, Medical School of Padova, Padova, Italy.
Clin Exp Metastasis. 2002;19(8):709-16. doi: 10.1023/a:1021302802297.
The effect of CNTF and BDNF on a proteolytic complement instrumental to invasion and on differentiation was studied in two murine neuroblastoma clones, N1 and N7. At the membrane level, gelatinase MMP-2--mainly the activated form--was restrained by CNTF and BDNF to a residual 34% with both factors; membrane-type 1 MMP was down-regulated to 50% (10 h) and 34% (24 h) with both factors; and urokinase-type plasminogen activator was restrained mainly by BDNF to 70%. In the medium, the two gelatinases MMP-2 and MMP-9 were mainly in zymogen form: only MMP-2 was restrained in N1 cells, while only MMP-9 was restrained in N7 cells by both factors, single or in combination. These effects were paralleled by the induction of neurite outgrowth, which was more stimulated in the less differentiated clone. These dose-dependent and transient effects make CNTF and BDNF ideal candidates for constraining the potentially invasive behavior of nervous system tumors.
在两个小鼠神经母细胞瘤克隆N1和N7中，研究了睫状神经营养因子（CNTF）和脑源性神经营养因子（BDNF）对一种有助于侵袭的蛋白水解补体以及分化的影响。在膜水平上，明胶酶MMP-2（主要是活化形式）在两种因子作用下均被CNTF和BDNF抑制至残余的34%；膜型1基质金属蛋白酶在两种因子作用下分别下调至50%（10小时）和34%（24小时）；尿激酶型纤溶酶原激活剂主要被BDNF抑制至70%。在培养基中，两种明胶酶MMP-2和MMP-9主要以酶原形式存在：在N1细胞中只有MMP-2受到抑制，而在N7细胞中两种因子单独或联合作用时只有MMP-9受到抑制。这些效应与神经突生长的诱导同时出现，在分化程度较低的克隆中神经突生长受到的刺激更大。这些剂量依赖性和短暂性效应使CNTF和BDNF成为抑制神经系统肿瘤潜在侵袭行为的理想候选物。
