1. The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma.
- Author
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Åström P, Juurikka K, Hadler-Olsen ES, Svineng G, Cervigne NK, Coletta RD, Risteli J, Kauppila JH, Skarp S, Kuttner S, Oteiza A, Sutinen M, and Salo T
- Subjects
- Aged, Animals, Apoptosis, Carcinoma, Squamous Cell chemistry, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell secondary, Cathepsin K metabolism, Cell Line, Tumor, Cell Movement drug effects, Cell Movement genetics, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Male, Matrix Metalloproteinase 1 metabolism, Matrix Metalloproteinase 8 analysis, Mice, Mice, Inbred BALB C, Middle Aged, Neoplasm Transplantation, Prognosis, Survival Rate, Tongue Neoplasms chemistry, Tongue Neoplasms genetics, Tongue Neoplasms pathology, Transforming Growth Factor beta1 pharmacology, Carcinoma, Squamous Cell metabolism, Matrix Metalloproteinase 8 genetics, Matrix Metalloproteinase 8 metabolism, Tongue Neoplasms metabolism, Transforming Growth Factor beta1 metabolism, Vascular Endothelial Growth Factor C metabolism
- Abstract
Background: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC)., Methods: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples., Results: MMP-8 reduced the invasion and migration of OTSCC cells and decreased the expression of MMP-1, cathepsin-K and vascular endothelial growth factor-C (VEGF-C). VEGF-C was induced by transforming growth factor-β1 (TGF-β1) in control cells, but not in MMP-8 overexpressing cells. In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival. TGF-β1 treatment also restored the migration of MMP-8 overexpressing cells to the level of control cells. In mouse tongue cancer, MMP-8 did not inhibit metastasis, possibly because it was eliminated in the peripheral carcinoma cells., Conclusions: The suppressive effects of MMP-8 in OTSCC may be mediated through interference of TGF-β1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.
- Published
- 2017
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