Differentiated expression of membrane type metalloproteinases (MMP-14, MMP-15) and pro-MMP2 in laryngeal squamous cell carcinoma. A novel mechanism.

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.