Hyaluronan and the hyaluronan synthases in cancer biology. Ha is present in interstitial collagenous matrices and increases viscosity and hydration. Both the synthesis and degradation of extracellular matrix are critical contributors to tissue repair and remodeling. Structure of human hyaluronidase1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. Paradoxically, both hyaluronan ha and hyaluronidases, the enzymes, isbn 9780123741783 buy the hyaluronan in cancer biology ebook. Paradoxically, both hyaluronan ha and hyaluronidases, the enzymes that eliminate ha, have also been correlated with cancer progression. Thus, in this special issue of glycobiology, it seems appropriate to discuss the biology of a glycosaminoglycan, called hyaluronic acid hyaluronan, or ha, that has become the most popular agent today for intradermal injections to improve wrinkles and other cosmetic defects. On the other hand, no significant differences were observed in pulmonary metastasis between the parental and mnngtreated cells fig. The rapid rate of discovery in hyaluronan biology has revealed the involvement of this glycosaminoglycan in fundamental processes in biology and biomedicine including cancer, regenerative medicine, stem cell survival, and inflammatory diseases. Hyaluronan, cancerassociated fibroblasts and the tumor microenvironment in malignant progression james b. Macrophages are essential to maintain tissue homeostasis. Hyaluronan, the main ligand for cd44, binds to and activates cd44 resulting in activation of cell.
The microenvironment provides a functional substratum supporting tumour growth. This chapter aims to bring attention to the field of ha and its role in cancer initiation, progression, and spread. University of toledo health science campus, biochemistry and cancer biology seminar toledo, oh, january 12, 2007, hyaluronan metabolism in prostate cancer progression 7. Therapeutic targeting of hyaluronan in the tumor stroma. The ip3 peptide contains a hyaluronanbinding motif, and fluoresceinlabeled ip3 peptide bound to immobilized hyaluronan in. Turley 2 1 department of laboratory medicine and pathology, masonic comprehensive cancer center, minneapolis, mn, united states. Two major approaches have been used to probe the involvement of hyaluronan. It covers the cell biology of hyaluronan in cancer, the role of hyaluronan receptors and signal transduction pathways and the clinical uses of hyaluronanrelated biomaterials as anticancer agents. Hyaluronan signaling and turnover, volume 123 1st edition. Hyaluronan is similar to the fluid that surrounds the joints in your body.
In other cancers, ha in the tumor matrix is overexpressed. Hyaluronan in cancer biology isbn 9780123741783 pdf epub. Hyaluronan histochemistrya potential new tool to assess. Pdf the role of hyaluronan in pancreatic cancer biology.
Hyaluronancell interactions are crucial in cancer progression. In many cancers of epithelial origin there is an upregulation of cd44, a receptor that binds ha. Fragmented hyaluronan accumulates during tissue injury and functions in ways distinct from. Paradoxically, both hyaluronan ha and hyaluronidases, the enzymes that eliminate ha, have also been. Hyaluronan side effects, dosage, interactions drugs. Jm is supported by chairmans fund professor in cancer research and funds from the pardee endowed chair in cancer biology. A large body of experimental evidence from animal models directly implicates hyaluronan in the progression of several tumor types. A biweekly scientific journal publishing highquality research in molecular biology and genetics, cancer biology, biochemistry, and related fields. Hyaluronancell interactions in cancer and vascular disease. Kosaki r, watanabe k, yamaguchi y 1999 overproduction of hyaluronan by expression of the hyaluronan synthase has2 enhances anchorageindependent growth and tumorigenicity. Highmolecularweight hmw hyaluronan, a major extracellular matrix component, is antioncogenic, whereas lowmolecularweight lmw hyaluronan is prooncogenic.
Purchase hyaluronan signaling and turnover, volume 123 1st edition. Hyaluronan in cancer biology university of toronto. Hyaluronan ha is a highmolecularmass glycosaminoglycan with diverse functions in tissue injury and repair, for instance, in inflammation and fibrogenesis. Cd44, a nonkinase transmembrane glycoprotein, is overexpressed in several cell types including cancer stem cells and frequently shows alternative spliced variants that are thought to play a role in cancer development and progression. Hyaluronan ha is a major component of this structure. A very simplified version of this scheme is presented in fig. Hyaluronan ha has been implicated in tissue remodeling, healing, and tumor growth. Analysis of serum hyaluronan is promising in the diagnosis of liver disease and various inflammatory conditions, e. Hyaluronan ha, an extracellular highmolecularmass polysaccharide, is supposed to be involved in the growth and progression of malignant tumours. Hyaluronan is a prominent component of the microenvironment in most malignant tumors and can be prognostic for tumor progression. With increasing recognition of the role of the tumor microenvironment in disease progression, stromal components of the tumor have become attractive targets for therapeutic intervention. Hyaluronan biology is being recognized as an important regulator of cancer progression.
Dissecting the dual nature of hyaluronan in the tumor. This almost magical substance appears to be a key regulator of. Hyaluronan, the main ligand for cd44, binds to and activates cd44 resulting in activation of cell signaling pathways that induces cell proliferation, increases. Pancreatic ductal adenocarcinoma is typically characterized by a dense desmoplastic stroma containing a large. Pancreatic ductal adenocarcinoma pdac remains the most deadly disease worldwide, with the lowest survival rate among all cancer types. Levels of ha surrounding tumor cells correlate with tumor aggressiveness 5. Hyaluronan in cancer biology ebook by 9780080921082. Extensive experimental evidence in animal models implicates hyaluronan interactions in tumor growth and metastasis, but it is also evident that a balance of synthesis and turnover by hyaluronidases is critical. J lesley department of cancer biology, the salk institute, san diego, california 921865800, usa. The aim of the present study was to investigate the relationships between the ha synthesizing and degrading enzymes in a spectrum of liver pathologies. Hmw hyaluronanmediated membrane cd44 clustering disrupts the hippo signalinginhibitory par1bmst complex to stimulate signaling, whereas lmw hyaluronan counteracts this by. Lim and colleagues demonstrate that perivascular lyve1expressing macrophages prevent arterial stiffness by controlling the expression of collagen in vascular smooth muscle cells, a process dependent on the engagement of lyve1 with hyaluronan on smooth muscle cells. While the role of ha in malignancy is welldefined, the mechanisms driving its biosynthesis in cancer are poorly understood. Hyaluronan is used to treat knee pain caused by osteoarthritis hyaluronan is usually given after other arthritis medications have.
Historically hyaluronan has been isolated from animal sources or extracted from bacteria, including strains of staphyloccus. Midwest connective tissue conference, chicago, il, october 2021, 2006 hyaluronan turnover promotes prostate cancer progression fourth omaha imaging symposium 8. Hyaluronan ha has long been recognized as essential to cancer biology. This fluid acts as a lubricant and shock absorber for the joints.
A major avenue whereby they influence tumor progression is most likely their role in the characteristics of cancer stem cells cscs, subpopulations of tumor cells that exhibit chemoresistance. Recent evidence suggests that hyaluronan ha, a major component of ecm, provides a favorable microenvironment for cancer progression. To investigate the roles of hyaluronan produced by cancer cells in cancer metastasis, the metastatic potential of the highly metastatic mouse mammary carcinoma fm3a ha1 cell line was compared with those of hyaluronandeficient mutant cells. The initial expansion of cancer cells generates a signal to create the cancer niche. Hyaluronan is a ubiquitous component of tissue ecm found in a native homeostatic form within hydrated tissues such as the vitreous of the eye, articular cartilage, synovial fluid, lymphatics, and skin. Threedimensional in vitro tumor models for cancer research and drug. Ha is a simple linear polymer in which a simple disaccharide is. Frontiers hyaluronan, cancerassociated fibroblasts and. This book is a must read for those interested in the role of hyaluronan and its receptors in cancer biology and therapy. The tumor stroma, consisting of nonmalignant cells and the extracellular matrix, undergoes significant quantitative and qualitative changes throughout malignant transformation and tumor progression. The role of hyaluronan in pancreatic cancer biology and therapy. Variant cell lines selected for alterations in the. A putative cellular scheme for ha catabolism was recently formulated stern, 2003, stern, 2004a. Hyaluronan has also been recognized in clinical medicine.
Hyaluronanbinding peptide for targeting peritoneal. Biochemistry and cell biology canadian science publishing. Recent studies have shown that hyaluronan strongly promotes anchorageindependent growth 37,42,63,64 and that the resistance of cancer cells to. The complex system involved in the synthesis, degradation and binding of the high molecular weight glycosaminoglycan hyaluronic acid hyaluronan or ha provides a variety of structures that can be exploited for targeted cancer therapy. The biology and role of cd44 in cancer progression. A concentrated solution of hyaluronan 10 mgml has, through its tissue protective and rheological properties, become a device in ophthalmic surgery. Hyaluronan signaling properties are unique among other biologically active molecules, that they are apparently not influenced by postsynthetic molecular modification, but by hyaluronan fragment size. Hyaluronan is a linear, unbranched polymer composed of alternating residues of. The eukaryotic translation initiation factor eif4e. Role of hyaluronan matrix in prostate cancer progression. Role of hyaluronan in pancreatic cancer biology and. Five different mutant clones showed markedly reduced hyaluronan production and lacked the ability to form hyaluronanrich pericellular coats. Hyaluronan is a highmolarmass linear glycosaminoglycan gag found intracellularly, on the surface of cells, but predominantly in the extracellular matrix ecm.
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