Interaction Between Hyaluronic Acid And Its Receptors Cd44 Rhamm Regulates The Activity Of Inflammation And Cancer

The biological outcome of Hyaluronan (also hyaluronic acid, abbreviated HA) interaction with its CD44 or RHAMM receptors recently attracted much attention within the scientific community owing to a Nature article by Tian X et al. (Nature 2013; 499:346-9). The article described a life span exceeding 30 years in naked mole rats, whereas the maximal lifespan of mice, to which the naked mole rat is related, is only 4 years. This observation is accompanied by the finding that the naked mole rat, in contrast to the mouse, does not develop spontaneous tumors during this exceptional longevity. The article provides evidence that interaction of long tissue HA (6000-12,000 kDa) of the naked mole rat with cell surface CD44, in contrast to the interaction of short tissue HA (less than 3000 kDa) with the mouse CD44, makes the difference. More specifically, this communication shows that the interaction of short HA with fibroblasts’ CD44 imposes on them susceptibility for malignant transformation, whereas the corresponding interaction with long HA imposes on the fibroblasts a resistance to malignant transformation. The article does not explain the mechanism that underlines these findings. However, the articles, that will be published in the proposed Research Topic in the Inflammation section of Frontiers in Immunology, can bridge not only this gap, but also may explain why interaction between short HA and cell surface CD44 (or RHAMM, an additional HA receptor) enhances the development of inflammatory and malignant diseases. Furthermore, the articles included in the proposed Frontiers Research Topic will show that cancer cells and inflammatory cells share several properties related to the interaction between short HA and cell surface CD44 and/or RHAMM. These shared properties include: 1. Support of cell migration, which allows tumor metastasis and accumulation of inflammatory cells at the inflammation site; 2. Delivery of intracellular signaling, which leads to cell survival of either cancer cells or inflammatory cells; 3. Delivery of intracellular signaling, which activates cell replication and population expansion of either cancer cells or inflammatory cells; and 4. Binding of growth factors to cell surface CD44 of cancer cells or inflammatory cells (i.e., the growth factors) and their presentation to cells with cognate receptors (endothelial cells, fibroblasts), leading to pro-malignant or pro-inflammatory activities. Going back to the naked mole rat story, we may conclude from the proposed articles of this Frontiers Research Topic that the long HA, which displays anti-malignant effect, interferes with the above described pro-malignant potential of the short HA (perhaps by competing on the same CD44 receptor). Extrapolating this concept to Inflammation, the same mechanism (competition?) may be valid for inflammatory (and autoimmune) activities. If this is the case, long HA may be used for therapy of both malignant and inflammatory diseases. Moreover, targeting the interaction between short HA and CD44 (e.g. by anti-CD44 blocking antibodies) may display also a therapeutic effect on both malignant and inflammatory diseases, an issue that encourages not only fruitful exchange of views, but also practical experimental collaboration.

The biological outcome of Hyaluronan (also hyaluronic acid, abbreviated HA) interaction with its CD44 or RHAMM receptors recently attracted much attention within the scientific community owing to a Nature article by Tian X et al. (Nature 2013; 499:346-9). The article described a life span exceeding 30 years in naked mole rats, whereas the maximal lifespan of mice, to which the naked mole rat is related, is only 4 years. This observation is accompanied by the finding that the naked mole rat, in contrast to the mouse, does not develop spontaneous tumors during this exceptional longevity. The article provides evidence that interaction of long tissue HA (6000-12,000 kDa) of the naked mole rat with cell surface CD44, in contrast to the interaction of short tissue HA (less than 3000 kDa) with the mouse CD44, makes the difference. More specifically, this communication shows that the interaction of short HA with fibroblasts' CD44 imposes on them susceptibility for malignant transformation, whereas the corresponding interaction with long HA imposes on the fibroblasts a resistance to malignant transformation. The article does not explain the mechanism that underlines these findings. However, the articles, that will be published in the proposed Research Topic in the Inflammation section of Frontiers in Immunology, can bridge not only this gap, but also may explain why interaction between short HA and cell surface CD44 (or RHAMM, an additional HA receptor) enhances the development of inflammatory and malignant diseases. Furthermore, the articles included in the proposed Frontiers Research Topic will show that cancer cells and inflammatory cells share several properties related to the interaction between short HA and cell surface CD44 and/or RHAMM. These shared properties include: 1. Support of cell migration, which allows tumor metastasis and accumulation of inflammatory cells at the inflammation site; 2. Delivery of intracellular signaling, which leads to cell survival of either cancer cells or inflammatory cells; 3. Delivery of intracellular signaling, which activates cell replication and population expansion of either cancer cells or inflammatory cells; and 4. Binding of growth factors to cell surface CD44 of cancer cells or inflammatory cells (i.e., the growth factors) and their presentation to cells with cognate receptors (endothelial cells, fibroblasts), leading to pro-malignant or pro-inflammatory activities. Going back to the naked mole rat story, we may conclude from the proposed articles of this Frontiers Research Topic that the long HA, which displays anti-malignant effect, interferes with the above described pro-malignant potential of the short HA (perhaps by competing on the same CD44 receptor). Extrapolating this concept to Inflammation, the same mechanism (competition?) may be valid for inflammatory (and autoimmune) activities. If this is the case, long HA may be used for therapy of both malignant and inflammatory diseases. Moreover, targeting the interaction between short HA and CD44 (e.g. by anti-CD44 blocking antibodies) may display also a therapeutic effect on both malignant and inflammatory diseases, an issue that encourages not only fruitful exchange of views, but also practical experimental collaboration.

Natural Biopolymers in Drug Delivery and Tissue Engineering systematically examines a broad range of natural polymers and their applications in drug delivery and tissue engineering. The book thoroughly collates the most relevant and up-to-date research on natural biopolymers, covering a variety of key natural polymer types such as chitin, chitosan, alginate, guar gum and collagen. It is divided into two sections, covering drug delivery and tissue engineering applications. Each section focuses on natural biopolymers in the form of scaffolds, membranes, films, gels and nanoparticles, thus helping the reader select not only the most appropriate polymer type, but also the most relevant structure. This comprehensive resource is ideal for materials scientists, biomedical engineers, tissue engineers, pharmaceutical scientists and anyone interested in developing novel materials for biomedical applications. Covers both drug delivery and tissue engineering applications of natural biopolymers, helping bridge the gap between the two Details a range of natural polymer types, ensuring all relevant options are presented Discusses the benefits, challenges and clinical translation of natural biopolymers

Biopolymeric Nanomaterials: Fundamentals and Applications outlines the fundamental design concepts and emerging applications of biopolymeric nanomaterials. The book also provides information on emerging applications of biopolymeric nanomaterials, including in biomedicine, manufacturing and water purification, as well as assessing their physical, chemical and biological properties. This is an important reference source for materials scientists, engineers and biomedical scientists who are seeking to increase their understanding of how polymeric nanomaterials are being used for a range of biomedical and industrial applications. Biopolymeric nanomaterials refer to biocompatible nanomaterials, consisting of biopolymers, such as protein (silk, collagen, gelatin, ß-casein, zein, and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch, and heparin). Biopolymeric nanomaterials may be used as i) delivery systems for bioactive compounds in food application, (ii) for delivery of therapeutic molecules (drugs and genes), or for (iii) tissue engineering. Provides information on the design concepts and synthesis of biopolymeric nanomaterials in biomedical and industrial applications Highlights the major properties and processing methods for biopolymeric nanomaterials Assesses the major challenges of producing biopolymeric nanomaterials on an industrial scale

This book covers the recent trends on the biological applications of nanomaterials, methods for their preparation, and techniques for their characterization. Further, the book examines the fundamentals of nanotoxicity, methods to assess the toxicity of engineered nanomaterials, approaches to reduce toxicity during synthesis. It also provides an overview of the state of the art in the application of Artificial intelligence-based methodologies for evaluation of toxicity of drugs and nanoparticles. The book further discusses nanocarrier design, routes of various nanoparticle administration, nano based drug delivery systems, and the toxicity challenges associated with each drug delivery method. It presents the latest advances in the interaction of nanoparticles with the cellular environment and assess nanotoxicity of these engineered nanoparticles. The book also explores the comparative and mechanistic genotoxicity assessment of the nanomaterials. This book is useful source of information for industrial practitioners, policy makers, and other professionals in the fields of toxicology, medicine, pharmacology, food, and drugs.

Multifunctional Hydrogels for Biomedical Applications Comprehensive resource presenting a thorough overview of the biomedical applications of hydrogels This book provides an overview of the development and applications of the clinically relevant hydrogels that are used particularly in tissue engineering, regenerative medicine, and drug delivery. Taking a multidisciplinary approach, it goes through the material from chemistry, materials science, biology, medicine, nanotechnology, and bioengineering points of view. Sample topics covered by the three well-qualified editors include: The design, functions, and developments of hydrogels Proteins and polysaccharides that mimic extracellular matrix Generation and applications of supramolecular hydrogels Design and functions of cell encapsulation systems Multifunctional Hydrogels for Biomedical Applications is a useful all-in-one reference work for materials scientists, polymer chemists, and bioengineers which provides a comprehensive, contemporary understanding of hydrogels and their applications targeting a wide variety of pathologies.

This book provides the whole spectrum of polysaccharides from basic concepts to commercial market applications. Chapters cover various types of sources, classification, properties, characterization, processing, rheology and fabrication of polysaccharide-based materials and their composites and gels. The applications of polysaccharides include in cosmetics, food science, drug delivery, biomedicine, biofuel production, marine, packaging, chromatography and environmental remediation. It also reviews the fabrication of inorganic and carbon nanomaterials from polysaccharides. The book incorporates industrial applications and will fill the gap between the exploration works in the laboratory and viable applications in related ventures.

A guide to state-of-the-art cancer immunotherapy in translational cancer research A volume in the Translational Oncology series, Immunotherapy in Translational Cancer Research explores the recent developments in the role that immunotherapy plays in the treatment of a wide range of cancers. The editors present key concepts, illustrative examples, and suggest alternative strategies in order to achieve individualized targeted therapy. Comprehensive in scope, Immunotherapy in Translational Cancer Research reviews the relevant history, current state, and the future of burgeoning cancer-fighting therapies. The book also includes critical information on drug development, clinical trials, and governmental resources and regulatory issues. Each chapter is created to feature: development of the immunotherapy; challenges that have been overcome in order to scale up and undertake clinical trials; and clinical experience and application of research. This authoritative volume is edited by a team of noted experts from MD Anderson Cancer Center, the world’s foremost cancer research and care center and: Offers a comprehensive presentation of state-of-the-art cancer immunotherapy research that accelerates the pace of clinical cancer care Filled with the concepts, examples, and approaches for developing individualized therapy Explores the breath of treatments that reflect the complexity of the immune system itself Includes contributions from a panel international experts in the field of immunotherapy Designed for physicians, medical students, scientists, pharmaceutical executives, public health and public policy government leaders and community oncologists, this essential resource offers a guide to the bidirectional interaction between laboratory and clinic immunotherapy cancer research.