Editorial [Hot Topic: Role of Carbohydrates in Tumour Progression, Metastasis and Anti-Tumour Drug Development (Guest Editor: Prof. Laura Cipolla)]

The role of carbohydrates in tumour progression, metastasis and anti-tumour drug development is nowadays evident. It is now well known that oligosaccharides found on cell surfaces play key roles in many and diverse recognition and adhesion processes both in physiological and pathological states. In particular, changes in glycosylation are often encountered in disease states. In the past decade advances in genomics, proteomics and mass spectrometry have enabled the association of specific glycan structures with disease states. The glycosylation pattern of a cell is therefore a code for cellular physiology. An understanding of this code at both molecular and functional levels is starting to emerge. The treatment of diseases such as cancer is extremely challenging because the pathology involves dysregulation of endogenous and often essential cellular processes. Effective therapies typically capitalize on differences between diseased and healthy tissues that can be targeted with drugs. The availability of novel molecular targets that distinguish diseased from healthy cells could vastly amplify therapeutic opportunities. In particular, cancer cells frequently display glycans at different levels or with fundamentally different structures than those observed on normal cells. This issue focuses on the different aspects involving carbohydrates in tumour progression, metastasis and antitumour drug development. Glycosylation changes are usually a hallmark of the tumour phenotype. Alterations in glycosylation in cancer is deeply reviewed by Brooks et al. Altered glycans patterns in cancer was corroborated with histological evidence that lectins show differential binding to healthy compared with malignant tissue. Raz and co-workers provide an overview of the link between glycan structures and disease progression, with a particular focus on the biological modulation by lectins and their ligands in tumor progression and metastasis. Galectins and selectins can play crucial biological roles in tumor cell-cell or cell-matrix interactions mediated by cell surface carbohydrate determinants and protein (lectin) binding as a cross-linker. Although it has long been appreciated that glycan expression changes with cellular condition, progress toward delineating the molecular basis of glycan function has been rather slow relative to comparable studies of proteins and nucleic acids. Due to the large number of possible structures, the information content of glycans is enormous. On consequence, description and characterisation of the molecular changes that occur upon malignant transformation is still a hard challenge. Opportunities to further illuminate tumour-associated glycan structures are offered by glycomics and NMR methods. Efforts towards the systematic study of the variations in cellular glycoconjugates are reviewed by Lara Mahal with particular attention to recent advances in glycosylation related technology, the latest mass spectrometry, microarray-based and computational technologies for glycomics. NMR-based structural studies of cancer-related glycidic structures for cancer drug developments are described by Jiménez-Barbero et al. with specific examples of medical significance in the cancer research field: a summary of spectroscopic methods for structural and conformational elucidation of bioactive carbohydrates based on nuclear magnetic resonance (NMR) is reviewed. Since the formation of carbohydrate-protein complexes is often the initial step of biological responses, knowledge about the structural factors that stabilize the complex may be relevant and contribute to predict the structural/conformational requirements of new drugs acting as agonists. An important step involved in metastasis is degradation of heparan sulfate proteoglycan, a carbohydrate-protein complex; in addition, heparanase level expression, an endoglucuronidase that cleaves heparan sulfate, correlates with metastatic potential of tumour cells. Ping outlines the functional roles and the corresponding molecular mechanisms of heparin, heparan sulfate and heparanase in cancer development and how this knowledge may pave the way for exploring remedies against tumour metastasis.......