Kong Lingfei, Li Qing, Wang Lifu, Liu Zhengguo, Sun Tingyi
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing hospital, Fourth Military Medical University, Xi'an, China.
Neuropathology. 2007 Dec;27(6):516-21. doi: 10.1111/j.1440-1789.2007.00818.x.
Local invasion of tumor cells is characteristic of most human glioma invasions. It is associated with increased motility and a potential to degrade the extracellular matrix. Matrix metalloproteinases (MMPs) have been proved to be a main process in local invasion of brain tumor. PRL-3 is a new protein tyrosine phosphatase which would also degrade the extracellular matrix and has been proved to be expressed in liver metastases derived from colorectal cancer. In this study, we sought to investigate the expression of PRL-3 in glioma tissues and investigate the relationship between MMPs (MMP2, MMP9, membrane-type matrix metalloproteinase 1 [MT1-MMP]) activity and expression in gliomas. The modifications of in situ hybridization of mRNA phosphatase of regenerating liver-3 (PRL-3) methods are preformed in the study of paraffin-embedded slides. The immunohistochemistry and gelatin zymography are used to detect the expression of PRL-3 and activity of MMPs. The results show that PRL-3 mRNA and antibody of PRL-3 are detected in glioma tissues mainly in grades IV and III, only a little in grade II, but not in normal brain tissue and glioma grade I. MMP2 and MMP9 are observed mainly in glioma tissues of grades IV and III in activity and expression. MT1-MMP protein is located in glioma tissues and vessel endothelial cells. This is the first report of detecting PRL-3 expression in gliomas, especially in grades III and IV, which may play an important role in progression of gliomas. PRL-3, MMP2 and MT1-MMP cooperatively contribute to gliomas invasion. Intermediate MMP2 (MT1-MMP, TIMP-2, MMP2 trimeric complex) is detected in high grades of glioma tissues by gelatin zymography and may be a marker indicating latent malignance of gliomas.
肿瘤细胞的局部侵袭是大多数人类胶质瘤侵袭的特征。它与细胞运动性增加以及降解细胞外基质的能力有关。基质金属蛋白酶（MMPs）已被证明是脑肿瘤局部侵袭的主要过程。PRL-3是一种新的蛋白酪氨酸磷酸酶，它也能降解细胞外基质，并且已被证实在结直肠癌肝转移灶中表达。在本研究中，我们试图研究PRL-3在胶质瘤组织中的表达，并探讨MMPs（MMP2、MMP9、膜型基质金属蛋白酶1 [MT1-MMP]）活性和表达与胶质瘤之间的关系。在石蜡包埋切片的研究中对再生肝-3（PRL-3）mRNA磷酸酶原位杂交方法进行了改进。采用免疫组织化学和明胶酶谱法检测PRL-3的表达和MMPs的活性。结果显示，PRL-3 mRNA和PRL-3抗体主要在IV级和III级胶质瘤组织中检测到，II级中仅有少量表达，而在正常脑组织和I级胶质瘤中未检测到。MMP2和MMP9主要在IV级和III级胶质瘤组织中观察到活性和表达。MT1-MMP蛋白位于胶质瘤组织和血管内皮细胞中。这是首次报道在胶质瘤中检测到PRL-3的表达，尤其是在III级和IV级，其可能在胶质瘤进展中起重要作用。PRL-3、MMP2和MT1-MMP共同促进胶质瘤的侵袭。通过明胶酶谱法在高级别胶质瘤组织中检测到中间型MMP2（MT1-MMP、TIMP-2、MMP2三聚体复合物），其可能是提示胶质瘤潜在恶性的一个标志物。
