There has been a dramatic increase in knowledge of tight junctions in the past decade. The molecular structure of tight junctions, cellular functions and the pathophysiological roles of tight junctions are becoming clear. Of the most important functions, the role of the cellular structure in cancer spread and drug delivery are increasingly realised. It is now clear that there are fundamental changes to tight junctions during the process of cancer development. Tight junctions are also critical to the metastatic process of cancer cells. The cellular structure is also crucial in drug therapies, namely, the permeability and bioavailability of the drugs, penetration of barriers such as the blood brain barrier. This current volume aims to summarise the current knowledge of tight junctions, their role in cancer and cancer metastasis and is of interest to scientists and clinicians.

This book provides an updated account of tight junctions of different epithelia and endothelia and addresses their anatomy, biochemistry, physiology, synthesis, assembly, and modulation. It also discusses the relationship between molecular structure, function, regulation, posttranslational modifications of tight junction proteins and their role in gut microbiota maintenance, epithelial-mesenchymal transition, and intestinal barrier dysfunction-associated disorders important for the progression of human cancers. This book presents the pathological alterations of tight junctions at the blood-brain barrier that intensify or even initiate neurological dysfunction. Further, it reviews the significance of tight junctions and tight junction proteins in cancer development, infectious diseases, allergic reactions, and autoimmune disorders. Lastly, it highlights strategies for modulating tight junctions to enhance drug availability and organ deposition. This book is immensely useful for basic, translational, clinical, and interdisciplinary cancer researchers, practicing oncologists, and immunologists.

This volume explores the dynamic topic of tight junctions. The book focuses on tight junctions' role in sealing adjacent epithelial cells in a narrow band just beneath their apical surface. The book explains how tight junctions consist of a network of claudins and other proteins, and delves into how they hold cells together and form functional and protective barriers, regulating the passage of molecules and ions through the space between cells. The book opens with a discussion of the evolution of research on tight junctions, discussing a range of primary areas of growth, including the current knowledge on the particular physiological function of different claudins due to the development of an array of knock out mice. The chapters also explore in-depth studies of tight junctions in specific tissues (gut, lung and endothelia). This book offers a comprehensive understanding on post-translational modifications of occludin and its impact on tight junction function, as well as the molecular composition and function of tricellular tight junctions. This volume is particularly relevant to students and scientists in neuroscience, cell biology, physiology, cell differentiation, and cancer research.

This book covers the molecular and cellular aspects of cancer metastasis, and discusses the clinical aspect of micro- and macro-metastases, which result in the death of the majority of patients with cancer. The current edition attempts to examine the current status of the basic scientific and clinical research in the area, and is a very useful reference for clinicians, oncologists, and biologists. It is intended for undergraduates as well as postgraduates in the area of medicine, oncology, and cancer biology.

Abstract: Tight junctions (TJs) are intercellular protein complexes that preserve tissue homeostasis and integrity through the control of paracellular permeability and cell polarity. Recent findings have revealed the functional role of TJ proteins outside TJs and beyond their classical cellular functions as selective gatekeepers. This is illustrated by the dysregulation in TJ protein expression levels in response to external and intracellular stimuli, notably during tumorigenesis. A large body of knowledge has uncovered the well-established functional role of TJ proteins in cancer pathogenesis. Mechanistically, TJ proteins act as bidirectional signaling hubs that connect the extracellular compartment to the intracellular compartment. By modulating key signaling pathways, TJ proteins are crucial players in the regulation of cell proliferation, migration, and differentiation, all of which being essential cancer hallmarks crucial for tumor growth and metastasis. TJ proteins also promote the acquisition of stem cell phenotypes in cancer cells. These findings highlight their contribution to carcinogenesis and therapeutic resistance. Moreover, recent preclinical and clinical studies have used TJ proteins as therapeutic targets or prognostic markers. This review summarizes the functional role of TJ proteins in cancer biology and their impact for novel strategies to prevent and treat cancer

gar discusses recent studies of the SF gene promoter that may be relevant to understanding the detailed molecular mechanism(s) by which soluble factors regulate SF production. Polverini and Nickoloff discuss another mechanism by which SF may enhance tumor growth, ie., stimulation of angiogenesis, the formation of new blood vessels from pre-existing microvessels. Angiogenesis is required for continued growth of most solid tumors, and provides a mechanism by which the stroma may continue to grow along with the tumor cells. Although endothelial cells are stromal cells, they express a number of epithelial characteristics including (i) epithelial-like tight junctions and junctional proteins; (ii) the ability to organize into flat­ tened tubular structures; (iii) the c-met receptor protein; and (iv) biologic responsiveness to SF. It is, perhaps, not surprising that vascular endothe­ lial cells may both produce and respond to SF in different situations. 'Epithelialness' may be defined in two ways: (i) expression of generic epithelial structures and proteins (eg., specialized junctions, junctional proteins [eg., cadherins, ZOl], cytokeratins); and (ii) production of specific differentiated products (eg., milk proteins by mammary epithelia, renin by renal tubular epithelia of the juxtaglomerular apparatus). Recent studies suggest that SF Ic-met signalling may mediate epithelia­ mesenchyme interconversion, in part by modifying some of the generic epithelial characteristics. Nusrat discusses the effects of SF on the epithelial junctional apparatus. Relatively little is known about whether and how SF regulates cell-specific differentiation.

The past twenty years have witnessed significant advances in the treatment of cancer by surgery and radiation therapy. Gains with cytotoxic chemotherapy have been much more modest. Of the approximately 900,000 newly diagnosed cases of cancer each year, 50010 result in death of the patient. The primary cause of these deaths is metastasis. Although the term metastasis was first coined by Recamier in 1829, only in the past ten years have there been intensive scientific investigations into the mechanisms by which tumor cells metastasize. What has emerged is a complex process of host-tumor cell interactions which has been termed the metastatic cascade. Due to the complexity of the metastatic process, the study of metastasis is multifaceted and involves elements of such areas as differentiation, en zymology, genetics, hematology, immunology, membrane biochemistry and molecular biology. The major objectives of this book were to present the most recent advances in our understanding of how tumor cells metastasize to secondary sites by the leading experts in the biology of tumor invasion and metastasis. We hope that this book will lead to new concepts for the treatment of subclinical metastatic cancer. The chapters in this book address both the basic science of metastasis and potential clinical therapies directed toward interruption of the metastatic cascade or toward eradication of subclinical metastases. Many relevant topics have been omitted due to space considerations and thus the topics included reflect the prej udices of the editors.