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 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.

Key Features

* 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


Graduate students, post-doctoral fellows, medical students, and researchers (oncologists, cell biologists, experimental biologists, and biochemists) working in the field of cancer research.

Table of Contents

Table of Contents Preface: Hyaluronan and Cancer Robert Stern Section I: Historical Overview 1.Association between “acid mucopolysaccharides” and malignancy: an old concept comes of age, finally Robert Stern Section II: Cell Biology of Hyaluronan in Cancer 2.Hyaluronan: a constitutive regulator of chemoresistance and malignancy in cancer cells Mark G. Slomiany and Bryan P. Toole 3.Growth factor regulation of hyaluronan deposition in malignancies Paraskevi Heldin, Eugenia Karousou, and Spyros S. Skandalis 4.HYALURONAN BINDING PROTEIN 1 (HABP1) IN CANCER BIOLOGY Kasturi Datta Section III: Hyaluronan Receptors and Signal Transduction Pathways 5.CD44 meets merlin and ezrin: Their interplay mediates the pro-tumor activity of CD44 and tumor-suppressing effect of merlin Ivan Stamenkovic and Qin Yu 6.Hyaluronan-mediated CD44 interaction with receptor and non-receptor kinases promotes oncogenic signaling, cytoskeleton activation and tumor progression Lilly Y.W. Bourguignon 7.Adhesion and penetration: two sides of CD44 signal transduction cascades in the context of cancer cell metastasis David J.J. Waugh, Ashleigh McClatchey, Nicola Montgomery, and Suzanne McFarlane 8.INVOLVEMENT OF CD44, A MOLECULE WITH A THOUSAND FACES, IN CANCER DISSEMINATION David Naor, Shulamit B. Wallach-Dayan, Muayad A. Zahalka, and Ronit Vogt Sionov 9.Rhamm/Hmmr: an intinerant and multifunctional hyaluronan binding protein th


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Academic Press
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About the author

Robert Stern

Robert Stern, MD, is Emeritus Professor, Department of Pathology, School of Medicine, University of California, San Francisco. Robert Stern left Germany in 1938 for Seattle, Washington. He graduated from Harvard College in 1957, and obtained the M.D. degree from the University of Washington (Seattle) in 1962, followed by a rotating internship at King County Hospital (Seattle). While a medical student, he worked in the laboratories of Drs. Krebs and Fisher, who became Nobel laureates. He received his resident training in Anatomic Pathology at the NCI, and was a research scientist at the NIH for 10 years. Since 1977, he has been a member of the Pathology Department at the University of California, San Francisco. He is a board-certified Anatomic Pathologist, participating in the research, teaching, administrative, and diagnostic activities of the Department. He directed the Ph.D. program in Experimental Pathology for ten years. For the past decade, his research has focused on hyaluronan and the hyaluronidases, an outgrowth of an interest in malignancies of connective tissue, stromal-epithelial interactions in cancer, and biology of the tumor extracellular matrix. His laboratory was the first to identify the family of six hyaluronidase sequences in the human genome. These enzymes were then sequenced, expressed, and characterized in his laboratory. Subsequent work has identified a catabolic pathway for hyaluronan.

Affiliations and Expertise

Emeritus, Department of Pathology, School of Medicine, University of California, San Francisco, USA


"For decades, hyaluronan researchers have followed with growing interest the slowly developing story of how cancer progression and metastasis are correlated with or regulated by hyaluronan and its catabolic degradation products. Initially trying to understand the role of hyaluronan metabolism in prostate, breast, melanoma and other carcinomas was a bit like the story of the blind men touching and describing an elephant, each with a different impression of what they found. Now, however, our understanding of how hyaluronan is related to cancer biology has come into much clearer focus and this is captured nicely in Hyaluronan in Cancer - a collection of well written research perspectives and summaries from ~20 research groups around the world. The timing of this volume edited by Dr. Stern is excellent - readers can now get an overview and understand the importance of hyaluronan in multiple cancers. The book provides the first state-of-the-field summary and should be a highly useful and cited source for cancer biologists and hyaluronan researchers for many years."

--Paul H. Weigel, Ph.D., Professor, Chairman George Lynn Cross Research Professor, Ed Miller Endowed Chair Biochemistry & Molecular Biology, The University of Oklahoma Health Sciences Center, College of Medicine, Oklahoma City, OK, USA

"Hyaluronan is a major component of the fluid extracellular matrix that surrounds cells and fills the intercellular spaces of tissue. Long known for its fundamental role in tissue development and physiology, hyaluronan’s involvement in cancer progression and metastasis has more recently become the subject of intense multidisciplinary efforts.

This volume provides a state-of-the-art review of hyaluronan’s role in the cell biology of cancer, its diagnostic and prognostic value, and its potential as a target for therapeutic intervention. Authored by leading researchers in the field, the chapters help bridge the gap between b