Department of Urology, Medical University of Białystok, 15-276 Białystok, Poland.
Department of Medical Biochemistry, Medical University of Białystok, ul. Mickiewicza 2, 15-089 Białystok, Poland.
Int J Mol Sci. 2024 Jul 25;25(15):8107. doi: 10.3390/ijms25158107.
Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity-both actual and specific-was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma.
膜型金属蛋白酶（包括 MMP-14 和 MMP-15）是参与细胞外基质成分降解的酶。在癌症中，它们参与细胞侵袭、血管生成和转移等过程。因此，本研究旨在评估 MMP-14 和 MMP-15 在人肾细胞癌中的表达、含量和活性。检查了 20 例健康肾组织样本（n=20）和 20 例透明细胞肾癌组织样本。使用 Western blot 和 ELISA 技术分别评估 MMP 的存在和含量。使用荧光分析评估其活性（实际活性和特异性活性）。正常人和癌症患者的肾组织中均存在 MMP-14 和 MMP-15 酶，且以高分子量复合物的形式存在。此外，这些酶以活性和潜伏形式存在。癌组织中的含量非常相似，但两种膜型金属蛋白酶的含量随着肾癌分级的增加而显著降低。更值得注意的是，在正常组织中，研究的酶中 MMP-14 的含量最高。考虑到实际和特异性活性结果，MMP-14 在所有研究组织中均优于 MMP-15。尽管如此，我们还注意到随着肾癌分级的增加，两种金属蛋白酶的活性均显著增强。两种酶的表达和活性均在所有检查的肾癌细胞组织中检测到。然而，我们的研究结果表明，跨膜金属蛋白酶 14（MMP-14）在研究的肾癌细胞组织中比 MMP-15 发挥更为重要和关键的作用。因此，MMP-14 似乎可以成为诊断、预后和治疗肾细胞癌的有前途的靶点。
