Background. Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential.Materials and Methods. This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined.Results. First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases.Conclusion. These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.
Sumary Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinomas and that may play a role in suppression of invasion and metastasis. We have shown previously that immunohistochemical staining for the major desmosomal glycoprotein, desmoglein (Dsg), is reduced in some cases of squamous cell carcinoma (SCC) of the head and neck, and that reduced staining correlates with lymph node involvement. Desmosomes are multicomponent organelles. We therefore sought to determine whether another major desmosomal mokcule, desmoplakin (Dp), showed similar reduced expression to that shown by desmoglein. We have stained 65 specimens of primary SCC of the oral cavity (37 non-metastatic and 28 metatastic) with monoclonal antibodies to both desmoglein and desmoplak-in. We show that reduction of Dp staining correlates with loss of differentiation of the primary tumour, degree of invasion and presence of lymph node metastases. Similar correlations were found with Dsg staining. There was also correlation between reduction in Dp staining and reduction in Dsg staining. It is concluded that down-regulation of desmosomal expression occurs in some cases of SCC of the oral cavity and is associated with invasion and metastasis. Desmosomes may have an invasion and metastasis suppressor function.
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