Expression of MMPs, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: Correlations with tumor invasion and metastasis

Background. Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the in vasion and metastasis of tumors. However, the detailed role of MMPs and TIM Ps (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 det ermine whether expression of MMPs on tumor cells is associated with such cl inicopathological features as the invasive and metastatic potential. Materials and Methods. This study included 96 cases of primary oral squamou s cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. Th e relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was imm unohistochemically examined. Results. First of all, a decrease in the staining of ECMs was observed in c ases with an increased expression of MMP-1, -2, and -9. The association bet ween the expression of MMPs and the loss of ECMs was thus found to be stati stically significant. Secondly, in both invasive and metastatic cases, a ma rked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. T he association of the expression of MMPs both with the mode of tumor invasi on and nodal involvement was thus found to be statistically significant. Th irdly, TIMP-2 was thus found not to significantly decrease in metastatic ca ses, while TIMP-1 expression significantly increased in metastatic cases. Conclusion. These results suggest that tumor progression is dependent on th e 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. (C) 1999 John Wiley & Sons, Inc.