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Chemokines are involved in cell migration and activation during routine immune surveillance, inflammation and even cancer metastasis. The migration of chemokine receptor-bearing cells, including leukocytes and tumor cells, occurs in response to the secretion of chemokines, which accumulate on cell surfaces through interaction with glycosaminoglycans (GAGs) where they effectively serve as traffic signals to guide cell movement. Engagement of chemokines with their receptors subsequently causes the activation of signaling pathways that result in firm adhesion and extravasation of the cell into tissue, and in the case of leukocytes, activation of defense mechanisms. However, in cancer cells, the signaling pathways can be exploited or redirected, resulting in responses like survival, growth and proliferation. Herein, a structural and functional approach was used to address specific questions about the interactions of chemokines (i) with GAGs and (ii) with chemokine receptors in the context of cancer. Technically, the use of mass spectrometry has been a strong theme throughout these studies. In Chapter 2, a novel application of hydroxyl radical footprinting coupled with mass spectrometry was used to characterize the GAG binding specificity of the chemokine, MCP-3/CCL7. Potential GAG binding epitopes, identified by mass spectrometry, were then validated by mutagenesis and functional assays. In Chapter 3 and 4, a phosphoproteomic mass spectrometry strategy was used to elucidate CXCL12-mediated survival signaling through the receptor, CXCR4, in cells from patients with chronic lymphocytic leukemia (CLL). While signaling cascades involved in chemokine-mediated migration are well established, pathways involved in cell survival and proliferation in cancer, are not. Methods developed for phosphopeptide enrichment, and subsequent analysis via mass spectrometry are described in Chapter 3, and interesting/novel phosphoproteins, potentially involved in CXCL12-mediated CLL survival are described in Chapter 4. In Chapter 5, a functional approach was taken to elucidate the roles of receptors CXCR4 and CXCR7 in breast cancer growth and metastasis. The data show that CXCR7 affects the functional activity of CXCR4 in vitro, and decreases the extent of lung metastases in vivo, without inhibiting primary tumor growth. Overall, these studies serve to better understand some of the regulatory mechanisms that control chemokine function in normal physiology and in cancer.
This detailed volume provides methods to guide assay development, procedures designed to investigate the chemokine and glycosaminoglycan (GAG) networks, as well as their interactions, in a wide range of organs and tissues in disease and in health. The initial chapters in this book present in vivo models used to examine the roles of chemokines and GAGs in normal physiology and in the pathophysiology of disease. The book then explores present cell- and tissue-based in vitro assays to examine chemokine:GAG interactions. Finally, analytic approaches are presented that provide assays for measuring GAGs, chemokines, and cellular responses. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Chemokine-Glycosaminoglycan Interactions: Methods and Protocols serves as an ideal guide for researchers seeking to analyze chemokine and GAG functions, interactions, and molecular mechanisms in vivo and in vitro.
Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.
This book is a printed edition of the Special Issue "Glycosaminoglycans and Proteoglycans" that was published in Pharmaceuticals
Mimicking the Extracellular Matrix approaches this topic from both basic science and practical engineering perspectives. Suitable for undergraduates, postgraduates, and academics, this text aims to unify the current knowledge of ECM biology and matrix-mimicking biomaterials.
Acute Rheumatic Fever and Rheumatic Heart Disease is a concise, yet comprehensive, clinical resource highlighting must-know information on rheumatic heart disease and acute rheumatic fever from a global perspective. Covering the major issues dominating the field, this practical resource presents sufficient detail for a deep and thorough understanding of the latest treatment options, potential complications, and disease management strategies to improve patient outcomes. - Divided into four distinct sections for ease of navigation: Acute Rheumatic Fever, Rheumatic Heart Disease, Population-Based Strategies for Disease Control, and Acute and Emergency Presentations. - International editors and chapter authors ensure a truly global perspective. - Covers all clinical aspects, including epidemiology, pathophysiology, clinical features, diagnosis, management, and treatment. - Includes key topics on population-based measures for disease control for effective primary, secondary, and tertiary prevention. - Consolidates today's available information and guidance into a single, convenient resource.
This book effectively links the latest scientific advances to current technological applications of polymers, mainly focusing on biodegradable polymers obtained from biomass. The individual chapters were written by academic and industry researchers alike, introducing readers to topics that have received little attention in the literature to date. Key topics covered include polymers used in various areas such as food packaging, pharmaceuticals, energy production and the cosmetics industry, as well as the treatment of aqueous effluents.
Although glycoproteins and proteoglycans have been a subject of re search for many years, it is only during the last five or so years that they have aroused the interest of a very broad cross section of investigators in the biological sciences. The reason for this expanded interest in these molecules is simple: not only are glycoproteins and proteoglycans ubiq uitous, but many are molecules with well-defined and important biological functions. The list of molecules that fall into this category grows daily; interferon, immunoglobulins, certain hormones, many cell surface recep tors, and viral coat proteins are but a few examples. Thus, investigators with interests as diverse as viral replication. cell-cell interactions. poly isoprenoid synthesis, secretory processes, hormone responses, embryonic development, and immunology have become concerned with glycopro teins and proteoglycans. The objective of this book is to summarize the current state of knowledge on the biochemistry of these molecules. Coverage is by no means encyclopedic; rather the thrust is to emphasize the recent ad vances. The first chapter deals primarily with structural work on the oligosaccharide chains of glycoproteins, but it will be apparent in it and in the succeeding two chapters on biosynthesis that not only do structural studies aid biosynthetic investigations, but that studies on biosynthesis often playa major role in elucidation of structure.