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 Postgraduate Education, Ministry of Health of the Russian Federation, Moscow, Russia.
Arkh Patol. 2017;79(6):36-42. doi: 10.17116/patol201779636-42.
to investigate the expression of the membrane-bound matrix metalloproteinase MT1-MMP (MMP-14), its tissue inhibitor TIMP-2, and the proMMP-14 activator furin in the corpus uteri from the vaginal wall to the bottom of the uterine cavity in squamous cell carcinoma of the cervix (SCCC).
Hysterectomy material was examined in patients with SCCC. Reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and enzyme assays were used.
In SCCC, higher levels of MMP-14 expression were established in tumor cells, as evidenced by IHC (+3) and RT-PCR. IHC showed that the expression of MMP-14 was absent or insignificant in the normal uterine endometrial and myometrial tissues. However, that of MMP-14 mRNA was also found in the normal tissues to the bottom of the uterine cavity. Furin activity in the tumor was much higher than that in normal tissues. IHC indicated that TIMP-2 expression was low or absent in both the tumor and normal tissues. The expression of TIMP-2 mRNA was sufficiently obvious in both the tumor and normal tissues to the bottom of the uterine cavity.
In SCCC, MMP-14 expression was substantially increased in tumors. The expression of MMP-14 and regulators of its activity is aimed at enhancing the tumor destructive (invasive) potential in the pericellular space and can occur (be induced) in the morphologically normal uterine tissue apparently with involvement of signaling through the epithelial-mesenchymal interaction. Data are important for understanding the role of MMP-14 in the development of a multistage process of carcinogenesis and may have prognostic value and an impact on therapeutic strategy for the patient.
研究膜结合基质金属蛋白酶MT1-MMP（MMP-14）、其组织抑制剂TIMP-2以及前MMP-14激活剂弗林蛋白酶在子宫颈鳞状细胞癌（SCCC）患者从阴道壁至子宫腔底部的子宫体中的表达情况。
对SCCC患者的子宫切除标本进行检查。采用逆转录聚合酶链反应（RT-PCR）、免疫组织化学（IHC）和酶活性检测方法。
在SCCC中，免疫组织化学（+3）和RT-PCR结果表明肿瘤细胞中MMP-14表达水平较高。免疫组织化学显示，正常子宫内膜和肌层组织中MMP-14表达缺失或不显著。然而，在子宫腔底部的正常组织中也发现了MMP-14 mRNA。肿瘤组织中的弗林蛋白酶活性远高于正常组织。免疫组织化学表明，肿瘤组织和正常组织中TIMP-2表达均较低或缺失。在肿瘤组织和子宫腔底部的正常组织中，TIMP-2 mRNA的表达均足够明显。
在SCCC中，肿瘤组织中MMP-14表达显著增加。MMP-14及其活性调节因子的表达旨在增强肿瘤细胞周围间隙的破坏（侵袭）潜能，并且可能（被诱导）发生在形态学上正常的子宫组织中，显然涉及上皮-间质相互作用的信号传导。这些数据对于理解MMP-14在多阶段致癌过程中的作用具有重要意义，可能具有预后价值并影响患者的治疗策略。
