Downregulation of metallothionein 2A reduces migration, invasion and proliferation activities in human squamous cell carcinoma cells

• Published in: Molecular biology reports 2022-05, Vol.49 (5), p.3665-3674
• Main Authors: Dias, Aline Marques, de Mendonça, Raíssa Pinheiro, da Silva Kataoka, Maria Sueli, Jaeger, Ruy G., de Jesus Viana Pinheiro, João, de Melo Alves Junior, Sérgio
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Cancer; Cell growth; Cell migration; Cell proliferation; Epidermal growth factor; Extracellular matrix; Gelatinase A; Gelatinase B; Histology; Immunofluorescence; Invasiveness; Life Sciences; Matrix metalloproteinase; Metalloproteinase; Metallothionein; Morphology; Oral cancer; Original Article; Proteolysis; siRNA; Squamous cell carcinoma; Transforming growth factor-a; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-022-07206-6

Background The invasive behaviour of squamous cell carcinoma (SCC), a common malignant tumour of the mouth, is a process mediated by cell proliferation, extracellular matrix proteolysis and other factors. Studies have shown a potential relationship between growth factors, metallothionein 2A (MT2A) and matrix metalloproteinase (MMP) activation in malignant tumours. The aim of this study was to downregulate MT2A in cells (Cal27) derived from human squamous cell carcinoma. Methods Cal27 cells with reduced MT2A were subjected to proliferation, migration and invasion assays. Immunofluorescence and western blot confirmed MT2A depletion by siRNA . Growth curve assays assessed cell proliferation. Indirect immunofluorescence analysed the expression of MT2A, MMP-2, MMP-9, epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), tumour necrosis factor alpha (TNF-α) and Ki67. Zymography evaluated the effects of MT2A silencing on MMP-2 and -9 expression. Migration and invasion activities were evaluated using migration and invasion assays. Results CAL27 cells displayed MT2A, MMP-2, MMP-9, EGF, TGF-α, TNF-α and Ki67. MT2A depletion decreased MMP-9, EGF, TGF-α and Ki67 protein levels, while increasing TNF-α. Conclusions MT2A downregulation reduced cell proliferation, migration and invasion activities. Therefore, MT2A has an important role in cell proliferation, migration and invasion in human oral SCC cells.