Membrane Type 1 Matrix Metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells

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.

Tetracycline Derivative Minocycline Inhibits Autophagy and Inflammation in Concanavalin-A-Activated Human Hepatoma Cells

“…In fact, high expression of NANOS1 was reported to correlate with low levels of E-cadherin and with aggressive tumor behavior 35,36. Interestingly, overexpression of MT1-MMP was recently demonstrated to induce both EMT processes associated with breast tumor progression37 and the generation of cells exhibiting cancer stem cells properties and decreased expression of E-cadherin 38. How NANOS1 induces invasiveness still remains unclear but has been, in part, associated with MT1-MMP upregulation 31.…”

Mechanisms of Invasion in Head and Neck Cancer

“…152 For proteases, MT1-MMP has been shown to induce EMT and stemlike properties in OSCC, as well as invasion, in parallel with increased levels of Twist and ZEB. 221 However, there may be subtypes of cancer stem cells, which differ in their invasive ability. 231 One aspect of invasion that needs more examination in HNSCC is collective invasion, in which cell-cell contacts may be maintained during invasion.…”

“…There are also changes in cellular proteins, such as integrins and a-smooth muscle actin, as well as ECM proteins, such as collagen, laminin, and fibronectin. 149,[213][214][215][216][220][221][222][223] The HNSCC cells that undergo EMT have been shown to be more invasive. * The loss of E-cadherin associated with EMT is an indicator of poor prognosis in HNSCC.…”

Impedimetric quantification of the formation process and the chemosensitivity of cancer cell colonies suspended in 3D environment

“…Bio-assay is to analyze the indicative cellular components and the result is objective. For quantification of cell colonies, colonies are broken up into individual cells and bio-assay is used for quantification in some research groups (Lee and Chang, 2015;Yang et al, 2013). In our study, WST-1 assay (Roche Applied Science, USA) was used to quantify the number of individual cells broken from colonies every 24 h. Because the reagent of WST-1 assay reacts with the respiratory chain of the mitochondria, i.e., only active in metabolically intact cells, the optical density of the reacted product directly correlates to the number of viable individual cells.…”