Membrane Type 1 Matrix Metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells
1 Department of Basic Science of Stomatology, Institute of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China
2 Department of Basic Science of Stomatology, College of Stomatology, Nanjing Medical University, Postal# 210029 136# Hanzhong Road, Nanjing, Jiangsu, People’s Republic of China
3 Department of Stomatology, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
4 Department of the First Outpatient, College of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China
5 Department of Oral and Maxillofacial Surgery, College of Stomatology, Nanjing Medical University, Nanjing, People’s Republic of China
BMC Cancer 2013, 13:171 doi:10.1186/1471-2407-13-171Published: 1 April 2013
Tissue invasion and metastasis are acquired abilities of cancer and related to the death in oral squamous cell carcinoma (OSCC). Emerging observations indicate that the epithelial-to-mesenchymal transition (EMT) is associated with tumor progression and the generation of cells with cancer stem cells (CSCs) properties. Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) is a cell surface proteinase, which is involved in degrading extracellular matrix components that can promote tumor invasion and cell migration.
In the current study, we utilized SCC9 cells stably transfected with an empty vector (SCC9-N) or a vector encoding human MT1-MMP (SCC9-M) to study the role of MT1-MMP in EMT development.
Upon up-regulation of MT1-MMP, SCC9-M cells underwent EMT, in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial markers (E-cadherin, cytokeratin18 and β-catenin) and an increased expression of mesenchymal markers (vimentin and fibronectin). We further demonstrated that MT1-MMP-induced morphologic changes increased the level of Twist and ZEB, and were dependent on repressing the transcription of E-cadherin. These activities resulted in low adhesive, high invasive abilities of the SCC9-M cells. Furthermore, MT1-MMP-induced transformed cells exhibited cancer stem cell (CSC)-like characteristics, such as low proliferation, self-renewal ability, resistance to chemotherapeutic drugs and apoptosis, and expression of CSCs surface markers.
In conclusion, our study indicates that overexpression of MT1-MMP induces EMT and results in the acquisition of CSC-like properties in SCC9 cells. Our growing understanding of the mechanism regulating EMT may provide new targets against invasion and metastasis in OSCC.