214 research outputs found
Membrane-type matrix metalloproteinases: expression, roles in metastatic prostate cancer progression and opportunities for drug targeting
YesThe membrane-type matrix metalloproteinases (MT-MMPs), an important subgroup of
the wider MMP family, demonstrate widespread expression in multiple tumor types, and
play key roles in cancer growth, migration, invasion and metastasis. Despite a large body
of published research, relatively little information exists regarding evidence for MT-MMP
expression and function in metastatic prostate cancer. This review provides an appraisal of
the literature describing gene and protein expression in prostate cancer cells and clinical
tissue, summarises the evidence for roles in prostate cancer progression, and examines
the data relating to MT-MMP function in the development of bone metastases. Finally, the
therapeutic potential of targeting MT-MMPs is considered. While MT-MMP inhibition
presents a significant challenge, utilisation of MT-MMP expression and proteolytic capacity
in prostate tumors is an attractive drug development opportunity
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Glycosyl disulfides: importance, synthesis and application to chemical and biological systems
YesThe disulfide bond plays an important role in the formation and stabilisation of higher order structures of peptides and proteins, while in recent years interest in this functional group has been extended to carbohydrate chemistry. Rarely found in nature, glycosyl disulfides have attracted significant attention as glycomimetics, with wide biological applications including lectin binding, as key components of dynamic libraries to study carbohydrate structures, the study of metabolic and enzymatic studies, and even as potential drug molecules. This interest has been accompanied and fuelled by the continuous development of new methods to construct the disulfide bond at the anomeric centre. Glycosyl disulfides have also been exploited as versatile intermediates in carbohydrate synthesis, particularly as glycosyl donors. This review focuses on the importance of the disulfide bond in glycobiology and in chemistry, evaluating the different methods available to synthesise glycosyl disulfides. Furthermore, we review the role of glycosyl disulfides as intermediates and/or glycosyl donors for the synthesis of neoglycoproteins and oligosaccharides, before finally considering examples of how this important class of carbohydrates have made an impact in biological and therapeutic contexts.The authors thank the Institute of Cancer Therapeutics (University of Bradford) Doctoral Training Centre for financial support
The Effect of Polysialic Acid Expression on Glioma Cell Nano-mechanics
YesPolysialic acid (PolySia) is an important carbohydrate bio-polymer that is commonly over-expressed on tumours of neuroendocrine origin and plays a key role in tumour progression. PolySia exclusively decorates the neural cell adhesion molecule (NCAM) on tumour cell membranes, modulating cell-cell interactions, motility and invasion. In this preliminary study, we examine the nano-mechanical properties of isogenic C6 rat glioma cells - transfected cells engineered to express the enzyme polysialyltransferase ST8SiaII, which synthesises polySia (C6-STX cells) and wild type cells (C6-WT). We demonstrate that polySia expression leads to reduced elastic and adhesive properties but also more visco-elastic compared to non-expressing wild type cells. Whilst differences in cell elasticity between healthy and cancer cells is regularly assigned to changes in the cytoskeleton, we show that in this model system the change in properties at the nano-level is due to the polySia on the transfected cell membrane surface
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