The interplay of matrix metalloproteinase-8, transforming growth factor-beta 1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

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Astrom , P , Juurikka , K , Hadler-Olsen , E S , Svineng , G , Cervigne , N K , Coletta , R D , Risteli , J , Kauppila , J H , Skarp , S , Kuttner , S , Oteiza , A , Sutinen , M & Salo , T 2017 , ' The interplay of matrix metalloproteinase-8, transforming growth factor-beta 1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma ' , British Journal of Cancer , vol. 117 , no. 7 , pp. 1007-1016 . https://doi.org/10.1038/bjc.2017.249

Title: The interplay of matrix metalloproteinase-8, transforming growth factor-beta 1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma
Author: Astrom, Pirjo; Juurikka, Krista; Hadler-Olsen, Elin S.; Svineng, Gunbjorg; Cervigne, Nilva K.; Coletta, Ricardo D.; Risteli, Juha; Kauppila, Joonas H.; Skarp, Sini; Kuttner, Samuel; Oteiza, Ana; Sutinen, Meeri; Salo, Tuula
Other contributor: University of Helsinki, Clinicum



Date: 2017-09-26
Language: eng
Number of pages: 10
Belongs to series: British Journal of Cancer
ISSN: 0007-0920
DOI: https://doi.org/10.1038/bjc.2017.249
URI: http://hdl.handle.net/10138/225784
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-beta 1 (TGF-beta 1) 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-beta 1 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-beta 1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.
Subject: matrix metalloproteinase-8
invasion
proteinase web
transforming growth factor-beta 1
vascular endothelial growth factor-C
squamous cell carcinoma
tongue neoplasms
LYMPH-NODE METASTASIS
STABLE EXTREMAL REGIONS
BREAST-CANCER CELLS
COLLAGENASE-2 MMP-8
PROGNOSTIC-SIGNIFICANCE
TUMOR MICROENVIRONMENT
EXPRESSION
PROGRESSION
FIBROBLASTS
INVASION
3122 Cancers
313 Dentistry
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