Abstract
Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, often presenting with recurrence and metastasis due to its high invasive capacity. Metallothionein (MT), a zinc storage protein that supplies this element for protease activity, is probably related to mucoepidermoid carcinoma behavior. This prompted us to characterize a cell line derived from mucoepidermoid carcinoma and to correlate metallothionein expression with transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs). Transcriptomic analysis and cytogenetic assays were performed to detect the expression of genes of interest and cellular chromosomal alterations, respectively. MEC cells with a depleted metallothionein 2A (MT2A) gene were subjected to Western blot to correlate metallothionein expression with growth factors and MMPs. Additionally, cells with depleted MT were subjected to migration and invasion assays. The transcriptomic study revealed reads mapped to cytokeratins 19 and AE1/AE3, α-smooth muscle actin, vimentin, and fibronectin. Cytogenetic evaluation demonstrated structural and numerical alterations, including the translocation t(11;19)(q21;p13), characteristic of MEC. Metallothionein depletion was correlated with the decreased expression of TGF-α and MMP-9, while TNF-α protein levels were augmented. Migration and invasion activity were diminished after metallothionein silencing. Our findings suggest an important role of MT in MEC invasion, through the regulation of proteins involved in this process.
Highlights
Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, representing about 30% of all salivary gland malignancies [1]
Cytokeratins presented reads mapped in the MEC cell line, mainly CK-7
Our findings suggest that metallothionein plays an important role in the tumor invasion mechanism in mucoepidermoid carcinoma, through the regulation of proteins directly involved in this process, such as transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs)-9
Summary
Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, representing about 30% of all salivary gland malignancies [1]. Growth factors promote the secretion of MMPs, providing a positive feedback mechanism favorable to tumor invasion [5] These events may occur with the contribution of metallothionein (MT), a low molecular weight and intracellular protein related to zinc storage [6]. MMPs are proteases responsible for tissue remodelling, especially the degradation of ECM components, including collagens, elastins, gelatin and proteoglycans [17], allowing the advancement of tumor cells into the bloodstream For this reason, they are considered essential for tumor invasion and metastasis in various neoplasms. We characterized a cell line derived from mucoepidermoid carcinoma and correlated the expression of metallothionein with transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs)
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