Abstract
BackgroundTissue 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.MethodsIn 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.ResultsUpon 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.ConclusionsIn 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.
Highlights
Tissue invasion and metastasis are acquired abilities of cancer and related to the death in oral squamous cell carcinoma (OSCC)
Human oral squamous cell carcinoma SCC9 cells are less aggressive, which may correlate with the low MT1MMP expression level observed in these cells
We utilized the up-regulation of MT1-Matrix metalloproteinase (MMP) in SCC9 cells, via the transfection of either an empty vector (SCC9-N) or a vector encoding human Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) (SCC9-M), to study the role of MT1-MMP in cancer invasion and metastasis
Summary
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. Tissue invasion and metastasis are exceedingly complex processes and are one of the hallmarks of cancer [3]; it is important to clarify the biological mechanism of. Researchers have shown that the EMT is associated with the dedifferentiation program that leads to malignant carcinoma [5], as the EMT confers invasive cancer cells an efficient migration ability and a selective advantage to reach distant locations [9,10]. Transcriptional repressor has recently emerged as a fundamental mechanism for the silencing of CDH1 (the gene that encodes E-cadherin), such as the Snail (Snail and Slug), ZEB (ZEB1 and ZEB2) and basic helix-loop-helix (bHLH: Twist) families [6,11]
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