Membrane Type 1 Matrix Metalloproteinase Regulating MMPs Expression Correlated With The Invasion And Metastasis In Oral Squamous Cell Carcinoma

Background:Oral squamous cell carcinoma (OSCC) is the most common oral cancer tumor in in head and neck carcinoma. The tumor cells from the primary tumor to distant organ were closely related to its poor prognosis. Matrix metalloproteinases, as the main components of extracellular matrix, have become one of the hot spots in the study of the occurrence, development, invasion and metastasis of tumors. As the first identification of membrane type matrix metalloproteinase, MT1-MMP has been reported to play an important role in tumor progression.Objective:In the current study, we aimed to analyze the expression of MT1-MMP and MMP2 in oral squamous cell carcinoma (OSCC) and their correlations with the clinical pathological characteristics, and to further identify the function of MT1-MMP in promoting cancer cell invasion and metastasis.Methods:1. The immunohistochemical staining method was used to investigate the expression of MT1-MMP and MMP2 in the tumor nest and tumor front in OSCC. The correlation of the MT1-MMP and MMP2 as well as the correlation of the MT1-MMP and MMP2 level with clinical pathological parameters, metastasis and prognosis were analyzed using the Chi Square analysis.1.The MT1-MMP miRNA interference vectors X-173-4 were transfected into SCC25 cells to obtain experiment group cells which down-regulate the express of MT1-MMP.2. The expression of MMP13, MMP9 and MMP2 in the control group and the experimental group were detected by real-time quantitative PCR and Western blot. The scratch test and Transwell assay were used to investigate the invasion and metastasis of the tumor. Finally, the degradation of the major components of MT1-MMP (FN) in ECM was analyzed by immunofluorescence assay.Results:Our results demonstrated that the high expression of MT1-MMP in tumors significantly correlated with the lymph node metastasis, pathological grade, recurrence and follow-up. The high expression of MMP2 in the tumor nest significantly correlated with the lymph node metastasis, clinical stage, pathological grade, recurrence and follow-up. In addition, the high expression of MMP2 at the invasive front of tumor significantly correlated with the lymph node metastasis, clinical stage, pathological grade, recurrence and follow-up. Furthermore, the patients with higher expression of MT1-MMP or MMP2 had shorter survival time in OSCC. Multivariate analysis indicated that MT1-MMP expression may serve as an independent prognostic indicator for the survival of patients with OSCC. In addition, MT1-MMP, through regulating associated MMPs expression, contributes to promoting the invasion and metastasis in oral cancer cells by degrading major ECM components.Conclusions:MT1-MMP may play an important role in OSCC invasion and metastasis and may act as a promising target for prognostic prediction.