Timoshenko O S, Gureeva T A, Kugaevskaya E V, Zavalishina L E, Andreeva Yu Yu, Solovyeva N I
V.N. Orekhovich Institute of Biomedical Chemistry, Moscow, Russia.
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia, Moscow, Russia.
Arkh Patol. 2018;80(6):22-28. doi: 10.17116/patol20188006122.
To investigate the expression of gelatinases A and B (matrix metalloproteinases (MMP 2 and MMP 9) and endogenous regulators of their activity, such as a tissue inhibitor of MMP - TIMP-2 and a Pro-MMP-9 activator - urokinase-type plasminogen activator (uPA) as factors of corpus uteri invasion in squamous cell cervical carcinoma (SCCC).
The surgical material obtained after hysterectomy in patients diagnosed with SCCC was examined. RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay were used.
In SCCC, the expressions of MMP 2 and MMP 9 were found to be high not only in carcinoma of the cervix uteri but also in the corpus uteri, which makes an additional contribution to the enhanced invasive potential of tumors and may have a prognostic value. In SCCC, the expression of MMP 9 may be induced in the corpus uteri where it was absent in normal conditions. MMP 9 can serve as a marker of an invasive process. In most cases, the activity of uPA in the tumor was significantly higher than that in intact uterine tissue, and the expression of TIMP-2 did not change substantially along the entire length of a tissue band (from the vaginal wall to the uterine fundus), as evidenced by RT-PCR, and was at a low level or absent, as shown by IHC. Impaired regulation of MMP 2 and MMP 9 expressions was found not only at the gene level, but also at post-translational one.
The expression of the gelatinases MMP 2, MMP 9 and regulators of their activity is aimed at increasing the tumor destructive (invasive) potential and can occur (be induced) in the intact corpus uteri tissue that is morphologically different from cervix uteri tissue with apparent participation of signaling through an epithelial-mesenchymal interaction. The induced MMP 9 can serve as a marker for invasive potential. The data indicate different tissue functions of MMP 2 and MMP 9. They are important for understanding the role of the gelatinases MMP 2, MMP 9 during carcinogenesis, can have a prognostic value, and affect a therapeutic strategy for patient management.
研究明胶酶A和B（基质金属蛋白酶（MMP - 2和MMP - 9））及其活性的内源性调节因子，如MMP组织抑制剂 - TIMP - 2和Pro - MMP - 9激活剂 - 尿激酶型纤溶酶原激活剂（uPA）作为子宫体浸润因素在宫颈鳞状细胞癌（SCCC）中的表达情况。
对诊断为SCCC的患者子宫切除术后获得的手术材料进行检查。采用逆转录聚合酶链反应（RT - PCR）、免疫组织化学（IHC）和酶联免疫吸附测定法。
在SCCC中，发现MMP - 2和MMP - 9不仅在子宫颈癌中高表达，在子宫体中也高表达，这对肿瘤侵袭潜能的增强有额外作用，且可能具有预后价值。在SCCC中，MMP - 9的表达可能在正常情况下不存在的子宫体中被诱导。MMP - 9可作为侵袭过程的标志物。在大多数情况下，肿瘤中uPA的活性显著高于完整子宫组织，RT - PCR证明TIMP - 2的表达在组织条带全长范围内基本未改变（从阴道壁到子宫底部），免疫组织化学显示其处于低水平或无表达。发现MMP - 2和MMP - 9表达的调节不仅在基因水平受损，在翻译后水平也受损。
明胶酶MMP - 2、MMP - 9及其活性调节因子的表达旨在增加肿瘤的破坏（侵袭）潜能，并且可以在形态上与子宫颈组织不同的完整子宫体组织中发生（被诱导），明显通过上皮 - 间充质相互作用参与信号传导。诱导产生的MMP - 9可作为侵袭潜能的标志物。这些数据表明MMP - 2和MMP - 9具有不同的组织功能。它们对于理解明胶酶MMP - 2、MMP - 9在致癌过程中的作用很重要，可能具有预后价值，并影响患者管理的治疗策略。
