Hyaluronan In Cancer Biology

Hyaluronan biology is being recognized as an important regulator of cancer progression. Paradoxically, both hyaluronan (HA) and hyaluronidases, the enzymes that eliminate HA, have also been correlated with cancer progression. Hyaluronan, a long-chain polymer of the extracellular matrix, opens up tissue spaces through which cancer cells move and metastasize. It also confers motility upon cells through interactions of cell-surface HA with the cytoskeleton. Embryonic cells in the process of movement and proliferation use the same strategy. It is an example of how cancer cells have commandeered normal cellular processes for their own survival and spread. There are also parallels between cancer and wound healing, cancer occasionally being defined as a wound that does not heal. The growing body of literature regarding this topic has recently progressed from describing the association of hyaluronan and hyaluronidase expression associated with different cancers, to understanding the mechanisms that drive tumor cell activation, proliferation, drug resistance, etc. No one source, however, discusses hyaluronan synthesis and catabolism, as well as the factors that regulate the balance. This book will offer a comprehensive summary and cutting-edge insight into Hyaluronan biology, the role of the HA receptors, the hyaluronidase enzymes that degrade HA, as well as HA synthesis enzymes and their relationship to cancer. * Offers a comprehensive summary and cutting-edge insight into Hyaluronan biology, the role of the HA receptors, the hyaluronidase enzymes that degrade HA, as well as HA synthesis enzymes and their relationship to cancer * Chapters are written by the leading international authorities on this subject, from laboratories that focus on the investigation of hyaluronan in cancer initiation, progression, and dissemination * Focuses on understanding the mechanisms that drive tumor cell activation, proliferation, and drug resistance

Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics. This volume covers hyaluronan signaling and turnover. Provides information on cancer research Outstanding and original reviews Suitable for researchers and students

This book addresses the structural and biological properties of the extracellular matrix component and glycosaminoglycan polymer hyaluronan (or hyaluronic acid, HA). The book discusses various aspects of HA biology, e.g., HA synthesis and degradation, as well as the role of HA in embryogenesis, development, and cell maintenance. The reader will learn about the role of HA in different tissues as well as its biological activities triggered by the interaction with different HA receptors. A closer look is had at the involvement of HA in human pathologies such as cancer, kidney fibrosis and wound healing. Biotechnological and biomedical applications for HA such as scaffold generation and drug delivery, including the novel synthetic sulphated HA are explored. This work will appeal to a wide readership within the extracellular matrix and hyaluronan field. It can serve as an introduction to the field for junior scientists but can also help senior scientists to gain a broader view of the field beyond their area of specialization. The series Biology of Extracellular Matrix is published in collaboration with the American Society for Matrix Biology and the International Society for Matrix Biology.

It was probably the French chemist Portes, who first reported in 1880 that the mucin in the vitreous body, which he named hyalomucine, behaved differently from other mucoids in cornea and cartilage. Fifty four years later Karl Meyer isolated a new polysaccharide from the vitreous, which he named hyaluronic acid. Today its official name is hyaluronan, and modern-day research on this polysaccharide continues to grow. Expertly written by leading scientists in the field, this book provides readers with a broad, yet detailed review of the chemistry of hyaluronan, and the role it plays in human biology and pathology. Twenty-seven chapters present a sequence leading from the chemistry and biochemistry of hyaluronan, followed by its role in various pathological conditions, to modified hylauronans as potential therapeutic agents and finally to the functional, structural and biological properties of hyaluronidases. Chemistry and Biology of Hyaluronan covers the many interesting facets of this fascinating molecule, and all chapters are intended to reach the wider research community. Comprehensive look at the chemistry and biology of hyaluronans Essential to Chemists, Biochemists and Medical researchers Broad yet detailed review of this rapidly growing research area

The aim of this book is to collect within one volume information on hyaluronan. This polysaccharide has received rapid attention for two reasons: it has important regulative functions within cell biology; and it has become a commercially important product because of its use in ophthalmic surgery and treatment of joint diease. A number of other practical applications are also discussed. The book covers various aspects of hyaluronan from the structure and chemistry of the polymer to its metabolism, cell biological interactions, behaviour in pathological processes, and potentially new medical applications.

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.

This volume provides an overview on the influence of Extracellular Matrix (ECM) on tumor progression. It covers topics such as signaling induced by structural ECM proteins including collagen and fibronectin, the control of ECM deposition and the turnover in tumors. Also discussed are the migration of cells through basement membranes and the function of proteoglycans including lumican and veriscan in tumor progression. Biomaterial-based in-vitro models as well as C. elegans models of the tumor microenvironment are used to show how these models can lead to a greater understanding of the disease mechanisms that promote cancer progression. The book addresses researchers working on cancer biology or ECM, and oncologists alike.

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.