Kachra Z, Beaulieu E, Delbecchi L, Mousseau N, Berthelet F, Moumdjian R, Del Maestro R, Béliveau R
Laboratoire de médecine moléculaire, Centre de cancérologie Charles-Bruneau, Hôpital Ste-Justine-UQAM, Montréal, Québec, Canada.
Clin Exp Metastasis. 1999;17(7):555-66. doi: 10.1023/a:1006760632766.
Sixty human brain tumors, classified according to the New World Health Organization (WHO) classification including, grade I schwannomas, meningiomas and pilocytic astrocytomas, grade II astrocytomas, grade III anaplastic astrocytomas, grade IV glioblastomas, grade III anaplastic oligodendrogliomas and grade IV glioblastomas and lung and melanoma metastases were analyzed for the expression of three matrix metalloproteinases (MMPs), two tissue inhibitors of MMPs (TIMPs) and for MMP activity. Some correlation was found between MMP expression and the degree of malignancy. Western blotting analysis revealed a more uniform pattern of distribution of MMP-2 (gelatinase A) than of MMP-9 (gelatinase B) and MMP-12 (metalloelastase) among tumors. MMP-9 levels were found to be significantly higher in grade III anaplastic astrocytomas and anaplastic oligodendrogliomas than those in grade I schwannomas and meningiomas. Anaplastic astrocytomas and Grade IV glioblastomas expressed significantly higher levels MMP-12 than grade I meningiomas. All sixty tumors showed a similar pattern of activity in zymography, proMMP-9 being the major species detected. Interestingly, TIMP-1 and TIMP-2 expression levels were especially low in tumors of grade II and grade III but significantly higher in tumors of grade I, particularly in schwannomas. Taken together, these data suggest that: 1) a balance between MMPs and TIMPs has an important role to play in human brain tumors; 2) TIMP expression may be valuable markers for tumor malignancy.
对60例人类脑肿瘤进行了分析，这些肿瘤根据世界卫生组织（WHO）新分类进行分类，包括I级神经鞘瘤、脑膜瘤和毛细胞型星形细胞瘤、II级星形细胞瘤、III级间变性星形细胞瘤、IV级胶质母细胞瘤、III级间变性少突胶质细胞瘤以及IV级胶质母细胞瘤和肺及黑色素瘤转移瘤，分析了三种基质金属蛋白酶（MMPs）、两种MMP组织抑制剂（TIMPs）的表达情况以及MMP活性。发现MMP表达与恶性程度之间存在一定相关性。蛋白质印迹分析显示，MMP-2（明胶酶A）在肿瘤中的分布模式比MMP-9（明胶酶B）和MMP-12（金属弹性蛋白酶）更为均匀。发现III级间变性星形细胞瘤和间变性少突胶质细胞瘤中的MMP-9水平显著高于I级神经鞘瘤和脑膜瘤。间变性星形细胞瘤和IV级胶质母细胞瘤中MMP-12的表达水平显著高于I级脑膜瘤。所有60个肿瘤在酶谱分析中显示出相似的活性模式，检测到的主要种类是前MMP-9。有趣的是，TIMP-1和TIMP-2的表达水平在II级和III级肿瘤中特别低，但在I级肿瘤中显著较高，尤其是在神经鞘瘤中。综上所述，这些数据表明：1）MMPs和TIMPs之间的平衡在人类脑肿瘤中起着重要作用；2）TIMP表达可能是肿瘤恶性程度的有价值标志物。
