Kudelski Jacek, Tokarzewicz Anna, Gudowska-Sawczuk Monika, Mroczko Barbara, Chłosta Piotr, Bruczko-Goralewska Marta, Mitura Przemysław, Młynarczyk Grzegorz
Department of Urology, Medical University of Bialystok, M. Skłodowskiej-Curie 24A St., 15-276 Białystok, Poland.
Department of Medical Biochemistry, Medical University of Białystok, Adama Mickiewicza 2C St., 15-089 Białystok, Poland.
Biomedicines. 2023 Mar 20;11(3):956. doi: 10.3390/biomedicines11030956.
Urinary bladder cancer is a serious oncological problem that is the cause of many deaths worldwide. The processes of metastasis and origination of local tumor invasion depend on the extracellular matrix (ECM) degradation. The cancer microenvironment, particularly the ECM, may be considered a key factor in cancer progression. Matrix metalloproteinases (MMPs) are classified as the main factors responsible for the degradation of ECM components. Therefore, the aim of the study was to evaluate the expression and activity of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) in urinary bladder cancer according to different stages.
Urinary bladder tissue samples were analyzed. Cancer patients were divided into two groups: low-grade tumors (LG; Group I) and high-grade tumors (HG; Group II). Control tissue was obtained from the opposite site to the tumor. MMPs content and activity (actual and specific) were evaluated using ELISA and Western blot methods, respectively.
Both MMPs are present in high and low molecular complexes in healthy or bladder cancer tissues. The content of MMP-9 is enhanced in comparison with MMP-2, particularly in HG cancer tissue. The actual activity of MMP-2 was highest in LG cancer tissue whereas the actual activity of MMP-9 was highest in HG cancer. Specific activity of both MMPs was highest in LG cancer, but the activity of MMP-9 was higher in comparison with MMP-2.
In conclusion, the content and specific activity of MMP-9 were increased in comparison with MMP-2. The revealed differences in content and activity of both MMPs demonstrate their different participation in ECM remodeling at different stages of cancer development. Moreover, it seems that MMP-9 has higher clinical utility than MMP-2 as a potential therapeutic option and a diagnostic biomarker of urinary bladder cancer.
膀胱癌是一个严重的肿瘤学问题，在全球范围内导致许多人死亡。转移过程和局部肿瘤侵袭的起源取决于细胞外基质（ECM）的降解。癌症微环境，尤其是细胞外基质，可被视为癌症进展的关键因素。基质金属蛋白酶（MMPs）被归类为负责细胞外基质成分降解的主要因素。因此，本研究的目的是根据不同阶段评估基质金属蛋白酶2和9（MMP - 2和MMP - 9）在膀胱癌中的表达和活性。
对膀胱组织样本进行分析。癌症患者分为两组：低级别肿瘤（LG；第一组）和高级别肿瘤（HG；第二组）。对照组织取自肿瘤相对的部位。分别使用酶联免疫吸附测定（ELISA）和蛋白质印迹法评估基质金属蛋白酶的含量和活性（实际活性和比活性）。
在健康或膀胱癌组织中，两种基质金属蛋白酶均以高分子和低分子复合物形式存在。与MMP - 2相比，MMP - 9的含量增加，特别是在高级别癌症组织中。MMP - 2的实际活性在低级别癌症组织中最高，而MMP - 9的实际活性在高级别癌症中最高。两种基质金属蛋白酶的比活性在低级别癌症中最高，但MMP - 9的活性相对于MMP - 2更高。
总之，与MMP - 2相比，MMP - 9的含量和比活性增加。两种基质金属蛋白酶在含量和活性上的差异表明它们在癌症发展的不同阶段对细胞外基质重塑的参与不同。此外，作为膀胱癌的潜在治疗选择和诊断生物标志物，MMP - 9似乎比MMP - 2具有更高的临床应用价值。
