Hyaluronan in Cancer Biology

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.

"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 basic science and clinical oncology, providing background and context that will prove valuable to both cancer and hyaluronan researchers for years to come." -- Philip A. Band, PhD, NYU Hospital for Joint Diseases, Department of Pharmacology, Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, USA"The link between the polysaccharide hyaluronan and cancer is well established. This excellent and comprehensive book brings together expert opinion for a thorough and up-to-date review of the topic. It covers the cell biology of hyaluronan in cancer, the role of hyaluronan receptors and signal transduction pathways and the clinical uses of hyaluronan-related biomaterials as anti-cancer agents. This book is a must read for those interested in the role of hyaluronan and its receptors in cancer biology and therapy." --Anthony J. Day, Faculty of Life Sciences, University of Manchester, UK

• Preface: Hyaluronan and CancerRobert Stern Section I: Historical Overview1.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 cellsMark G. Slomiany and Bryan P. Toole 3.Growth factor regulation of hyaluronan deposition in malignanciesParaskevi Heldin, Eugenia Karousou, and Spyros S. Skandalis4.HYALURONAN BINDING PROTEIN 1 (HABP1) IN CANCER BIOLOGYKasturi Datta Section III: Hyaluronan Receptors and Signal Transduction Pathways5.CD44 meets merlin and ezrin: Their interplay mediates the pro-tumor activity of CD44 and tumor-suppressing effect of merlinIvan Stamenkovic and Qin Yu6.Hyaluronan-mediated CD44 interaction with receptor and non-receptor kinases promotes oncogenic signaling, cytoskeleton activation and tumor progression Lilly Y.W. Bourguignon7.Adhesion and penetration: two sides of CD44 signal transduction cascades in the context of cancer cell metastasisDavid J.J. Waugh, Ashleigh McClatchey, Nicola Montgomery, and Suzanne McFarlane8.INVOLVEMENT OF CD44, A MOLECULE WITH A THOUSAND FACES, IN CANCER DISSEMINATIONDavid Naor, Shulamit B. Wallach-Dayan, Muayad A. Zahalka, and Ronit Vogt Sionov9.Rhamm/Hmmr: an intinerant and multifunctional hyaluronan binding protein that modifies CD44 signaling and mitotic spindle formation. James B. McCarthy and Eva A. TurleySection IV: Hyaluronan Synthesis10.Altered hyaluronan biosynthesis in cancer progressionNaoki Itano and Koji Kimata Section V: Hyaluronan Degradation, the Hyaluronidases, and the Products of Degradation11.HYALURONDIASE: BOTH A TUMOR PROMOTER AND SUPPRESSORVinata B. Lokeshwar and Marie G. Selzer12.The hyaluronidases in cancer biologyRobert Stern13.Hyaluronan fragments: informational polymers commandeered by cancersKazuki N. SugaharaSection VI : Hyaluronan in Cancer Epithelial-Stromal Interactions14.Hyaluronan in human tumors: importance of stromal and cancer cell-associated hyaluronanRaija H. Tammi , Anne H. Kultti, Veli-Matti Kosma, Risto Pirinen, Päivi Auvinen, and Markku I. Tammi15.THE ONCOFETAL PARADIGM REVISITED: MSF AND HA AS CONTEXTUAL DRIVERS OF CANCER PROGRESSIONSeth L. Schor, Ana M. Schor, Ian R. Ellis, Sarah J. Jones, Margaret Florence, Jacqueline Cox, and Anne-Marie Woolston Section VII: Hyaluronan and Individual Cancers16.Hyaluronan synthesis and turnover in prostate cancer Melanie A. Simpson 17.Role of hyaluronan in melanoma progressionCarl Gebhardt, Marco Averbeck, Ulf Anderegg, and Jan C. Simon 18.Role of Hyaluronan metabolism in the initiation, invasion and metastasis of Breast cancerTracey J. Brown and Natalie ThomasSection VIII: Clinical Uses of Hyaluronan-Related Biomaterials as Anti-Cancer Agents 19. Clinical application of hyaluronidase in combination cancer chemotherapy: a historic perspectiveGerhard Baumgartner and Gerhard Hamilton20.Exploring the hyaluronan-CD44 interaction for cancer therapyVirginia M. Platt and Francis C. Szoka Section IX: A New Perspective21.Hyaluronidase-2 and its role as a cell-entry receptor for sheepretroviruses that cause contagious respiratory tract cancersA. Dusty Miller