层粘连蛋白、基质金属蛋白酶-2及基质金属蛋白酶组织型抑制物-2在人脑胶质瘤侵袭性中的作用及相互关系

目的　分析层粘连蛋白 (LN)、基质金属蛋白酶 2 (MMP 2 )及基质金属蛋白酶组织型抑制物 2 (TIMP 2 )在人脑胶质瘤侵袭性中的作用和相互关系 ,探讨胶质瘤侵袭的分子机制。方法　用免疫组织化学SP法及原位杂交技术检测LN、MMP 2和TIMP 2在脑胶质瘤、颅内转移瘤及正常脑组织的表达情况。结果　LN和MMP 2的表达随着胶质瘤恶性程度的增加而增加 (P <0 0 1) ,TIMP 2的表达从正常 ,低级别 ,高级别到转移瘤组依次减少 ( χ2 =7 3736 ,P <0 0 1) ;MMP 2 /LN比值在颅内转移瘤中显著高于其它各组 (P <0 0 5 ) ,其它各组间无统计学差异 ,该值相对恒定 ;MMP 2 /TIMP 2比值随着胶质瘤恶性程度的增加而增加 ,在颅内转移瘤中显著高于其它各组 (P <0 0 5 )。结论　抗转移 (LN及TIMP 2 )和促转移 (MMP 2 )分子之间的平衡转化使得胶质瘤呈现出沿血管壁广泛浸润迁移却不破坏血管壁转移到颅外的生物学特性。

Roles of LN, MMP-2 and TIMP-2 in the Invasion of Human Gliomas and Their Relationship

Objective To investigate the mechanism of the infiltration and metastases of human gliomas by analyzing the role of laminin, MMP 2 and TIMP 2 in the invasion of human gliomas and their relationship.Methods The expression of laminin, MMP 2 and TIMP 2 in different groups including normal brain tissues, low grade gliomas, high grade gliomas and brain metastases were detected by using SP immunohistochemical staining. At the same time, in situ hybridization (ISH) was performed to examine the mRNA levels of MMP 2 and TIMP 2 in those tissues. Results SP immunohistochemical assay revealed that laminin was mainly expressed in the basement membrane of blood vessels, MMP 2 predominantly existed in cytoplasm of tumor cells around blood vessels besides the endothelial cells of blood vessels and TIMP 2 was also mostly immunostained in tumor cells and occasionally in the endothelial cells of blood vessels within tumor tissues. The level of LN and MMP 2 was increased with the increased gliomas grade ( P <0 01). The expression of TIMP 2 was decreased when the gliomas grade gradually augmented and was distinctly lower in brain metastases than in the other three groups ( P <0 0 1). MMP 2/LN ratio was by far lower in brain metastases ( P <0 05), but had no significant difference among the other groups. MMP 2/TIMP 2 ratio was increased as the enhancement of gliomas grade ( P <0 05). MMP 2/TIMP 2 was also obviously higher in brain metastases than in gliomas and normal brain tissues. The result by ISH was accordant with that obtained through ICH. Conclusion The overexpression of laminin is closely implicated in barrier that keeps gliomas from metastasizing to sites outside the neuraxis. MMP 2 plays a crucial role in gliomas invasion on the basis of an imbalanced TIMP 2.