期刊
EXPERIMENTAL CELL RESEARCH
卷 411, 期 1, 页码 -出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112984
关键词
Oral squamous cell carcinoma (OSCC); Invasion/ metastasis; MMP-2; ERK1/2; NF?B; AP1; Sp1; Twist
资金
- KKP (CSIR (Council for Scientific and Industrial Research, Govt. of India) ) fellowship
- DBT (Department of Biotechnology, Govt. of India) [BT/PR9028/INF/22/193/2013]
- [2014-19]
This study found that overexpression and activation of MMP-2 are associated with invasion and metastasis of oral squamous cell carcinoma (OSCC). Treatment with MEK inhibitor and ECGC can reduce MMP-2 activity and may be used as a therapeutic strategy to control invasive OSCC.
Background: Loco-regional invasion is commonly found in oral squamous cell carcinoma (OSCC) and is associated with its poor survival rate. Matrix metalloproteinase-2 (MMP-2) has been implicated in OSCC progression, but its regulation is poorly understood. Materials and methods: Here, one hundred twenty-seven different post-operated human oral cancer tissue samples were analyzed. The messenger RNA (mRNA) expression, protein expression, and MMP-2 activity and MT1-MMP, TIMP-2, and TFs (NF kappa B, AP1, Sp1, and Twist) were observed semi-quantitative RT-PCR, western blotting, and gelatin zymography. In addition, OSCC derived Cal-27, SCC4/9 cells, photochemical ECGC, and MAPK-pathway inhibitor PD98059 were utilized for in vitro testing and wound healing assay. Result: s: Increased protein and activity level of MMP-2 was detected in non-invasive (N0) and invasive (N1-3) oral tumors as compared to the control (adjacent normal) samples. MMP-2 protein and mRNA expression were positively associated with the TFs and MT1-MMP, negatively associated with TIMP-2 expression. Similarly, the MMP-2 expression/activity was related to several signal-transduction pathways like ERK1/2 and wnt-beta-catenin pathways. Treatment of ECGC/MEK inhibitor (PD98059) diminished MMP-2 activity and invasion/migration potential in OSCC. Conclusion: Our research suggests that the ERK1/2 driven overexpression/activation of MMP-2 was linked with the overall OSCC invasion and metastasis. Treatment of MEK inhibitor (PD98059) and ECGC diminished MMP-2 activity and thus could be exploited as a therapeutic strategy to control the invasive OSCC.
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