Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
J Oral Pathol Med. 2013 Mar;42(3):267-74. doi: 10.1111/jop.12000. Epub 2012 Sep 23.
Cancer progression involves multiple proteolytic interactions, with metalloproteinases (MMPs) performing a crucial role. MMP-2, a major MMP, plays a key role in the degradation of basement membranes. Mechanisms underlying MMP-2 activation had to be investigated. Membrane-type matrix metalloproteinases are not only responsible for the regulation of extracellular matrix remodeling, but also involved in the activation of several inactive MMPs. The aim of this study was to evaluate the expression of pro-MMP2, MMP-14, and MMP-15 in tumor cells and tumor stroma. Immunohistochemical studies were performed on paraffin-embedded tissue sections including laryngeal squamous cell carcinoma (SCC). We found the expression of pro-MMP2 in 58% of cases, MMP-14 in 78%, and MMP-15 in 98% of cases of SCC. In all tumor cases, we revealed a higher expression of pro-MMP2 in tumor stoma than in tumor cells. The expression of MMP-14 and MMP-15 was higher in tumor cells than in the stroma. Moreover, we found a statistically significant difference between the expression of MMP-14 and MMP-15 in the tumor in comparison with the surrounding stroma (P < 0.05). An analysis of expression levels of MT-MMPs by classification trees showed that the probability of metastases was related to decreased expression of MMP-14 and increased expression of MMP-15. Our results may suggest that tumor cells with low MMP-14 expression invade tumor stroma and form metastases. Probably, in such cases, tumor progression is stimulated by MMP-15 in an MMP-14 independent pathway, a novel (alternative) mechanism.
癌症的进展涉及多种蛋白水解相互作用，其中金属蛋白酶（MMPs）起着至关重要的作用。MMP-2 是一种主要的 MMP，在基底膜的降解中起着关键作用。必须研究 MMP-2 激活的机制。膜型基质金属蛋白酶不仅负责调节细胞外基质重塑，还参与几种无活性 MMP 的激活。本研究旨在评估肿瘤细胞和肿瘤基质中 pro-MMP2、MMP-14 和 MMP-15 的表达。对包括喉鳞状细胞癌（SCC）在内的石蜡包埋组织切片进行了免疫组织化学研究。我们发现 SCC 中 pro-MMP2 的表达率为 58%，MMP-14 为 78%，MMP-15 为 98%。在所有肿瘤病例中，我们发现肿瘤基质中 pro-MMP2 的表达高于肿瘤细胞。MMP-14 和 MMP-15 的表达在肿瘤细胞中高于基质。此外，我们发现 MMP-14 和 MMP-15 在肿瘤中的表达与周围基质之间存在统计学上的显著差异（P < 0.05）。通过分类树分析 MT-MMPs 的表达水平表明，转移的概率与 MMP-14 表达降低和 MMP-15 表达增加有关。我们的结果可能表明，MMP-14 表达降低的肿瘤细胞侵袭肿瘤基质并形成转移。可能在这种情况下，肿瘤进展是由 MMP-15 刺激的，这是一种新的（替代）机制。
