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

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.Peer reviewe

Fostering EfS Connections for Community Wellbeing: Working Meaningfully with What We’ve Got

This book fills an important gap in the literature, and presents contributions from scientists and researchers working in the field of sustainable development who have engaged in dynamic approaches to implementing sustainability in higher education. It is widely known that universities are key players in terms of the implementation and further development of sustainability, with some having the potential of acting as “living labs” in this rapidly growing field. Yet there are virtually no publications that explore the living labs concept as it relates to sustainability, and in an integrated manner. The aims of this book, which is an outcome of the “4th World Symposium on Sustainable Development at Universities” (WSSD-U-2018), held in Malaysia in 2018, are as follows: i. to document the experiences of universities from all around the world in curriculum innovation, research, activities and practical projects as they relate to sustainable development at the university level;ii. to disseminate information, ideas and experiences acquired in the execution of projects, including successful initiatives and good practice;iii. to introduce and discuss methodological approaches and projects that seek to integrate the topic of sustainable development in the curricula of universities; andiv. to promote the scalability of existing and future models from universities as living labs for sustainable development.The papers are innovative, cross-cutting and many reflect practice-based experiences, some of which may be replicable elsewhere. Also, this book, prepared by the Inter-University Sustainable Development Research Programme (IUSDRP) and the World Sustainable Development Research and Transfer Centre (WSD-RTC), reinforces the role played by universities as living labs for sustainable development

Lysyl hydroxylase 3 localizes to epidermal basement membrane and Is reduced in patients with Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention