Altered hyaluronan biosynthesis in cancer progression. Pancreatic ductal adenocarcinoma pdac remains the most deadly disease worldwide, with the lowest survival rate among all cancer types. The myriad of shorter ha chains occurs with activities that appear to be size specific. Decorin and hyaluronan ha represent vital ecm macromolecules in the microenvironment of cells and are centrally involved in human cancer and cardiovascular biology. Hyaluronan in cancer biology enhanced edition on apple. Hyaluronan ha is the only nonsulphated glycosaminoglycan of extracellular matrix. Simpson, hyaluronan synthesis and turnover in prostate cancer, hyaluronan in cancer biology, 10.
Molecular weight specificity of hyaluronan effects in cell biology, authorj. Fragmented hyaluronan accumulates during tissue injury and functions in ways distinct from. Hyaluronan biology is being recognized as an important regulator of cancer progression. The interaction of hyaluronan with matrix hyaluronan binding proteins and cellsurface hyaluronan receptors regulates many aspects of cell behavior such as cell migration, cellcell adhesion, and. Hyaluronan cd44 interactions and chemoresistance in cancer cells.
Although there has been considerable interest in the possible role of. Pdf biology and biotechnology of hyaluronan manuela viola. Advances in integrative anatomy and evolutionary biology, an official publication of the american association of anatomists, publishes new discoveries in the morphological aspects of molecular, cellular, systems, and evolutionary biology. The discovery of hyaluronan synthase has genes, which encode the key enzymes in hyaluronan biosynthesis, has enabled great strides in. Hyaluronan in cancer biology ebook por 9780080921082. Biology and biotechnology of hyaluronan springerlink. Review article role of hyaluronan in pancreatic cancer biology and therapy. In this article we discuss the influences of hyaluronan on disease progression.
Tissue hyaluronan expression, as reflected in the sputum. Dissecting the dual nature of hyaluronan in the tumor. Cancer research hyaluronan deficiency in tumor stroma. Hyaluronan and human endothelial cell behavior semantic scholar. Binding of ha to cd44 has been shown to activate mapk, rac, and phosphoinositide 3kinase pi3k signaling, leading to. Lung cancer lc is the major cause of death among other types of cancer in the world.
Hyaluronancell interactions in cancer and vascular disease. Hyaluronan is a highmolarmass linear glycosaminoglycan gag found intracellularly, on the surface of cells, but predominantly in the extracellular matrix ecm between cells. Tissue hyaluronan expression, as reflected in the sputum of. Cluster of differentiation44 cd44 is a ubiquitously present glycoprotein on the surface of mammalian cells that plays a significant role in a number of biological functions. Hyaluronan, a longchain polymer of the extracellular matrix, opens up tissue spaces through which cancer cells move and metastasize. Apr 11, 2019 hyaluronan, being at the crossroads of so many cellular pathways critical to cancer biology, needs to be investigated in depth. Recent evidence suggests that hyaluronan ha, a major component of ecm, provides a favorable microenvironment for cancer progression. Human hyaluronic acid synthase1 promotes malignant. It can exist in a proteinbound state with aggregating proteoglycans, where it expands the extracellular matrix and modulates cellcell interactions. Pdf biology and biotechnology of hyaluronan manuela. Alterations in hyaluronan metabolism, distribution, and function have been documented in many diseases, e.
Molecular biology and clinical laboratory, shanghai jiao tong university af. Hyaluronan presence, dimension, and strategic accumulation demands close scrutiny especially in understanding the molecular mechanisms by which different forms of hyaluronan affect cancer progression and chemoresistance. Regulation of cancer cell functions by hyaluronan hareceptor interactions. This book is a must read for those interested in the role of hyaluronan and its receptors in cancer biology and therapy. Cd44 can be activated to function as an hyaluronic acid. Hyaluronan biology in vocal fold morphology and biomechanics s. It can occur as a highmolecularweight hmw polymer, reaching 10 7 da, but also exists in much smaller forms. Pdf modulation of hyaluronan production by cd44 positive. While fibrillar collagen is a major component of fibrotic stroma, many additional prognostic ecm factors impact the biological and biomechanical. Hyaluronan arrests human breast cancer cell growth by prolonging. Hyaluronan, a longchain polymer of the extracellular matrix, opens up tis. Ijc international journal of cancer modulation of hyaluronan production by cd44 positive glioma cells marzenna wiranowska1, sharron ladd1, lynn c.
Despite these caveats, it is clear that hyaluronan cd44 interactions are an impor. Moscinski1,2, bobbye hill2, ed haller1, katalin mikecz3 and anna plaas4 1 department of pathology and cell biology, university of south florida, college of medicine, tampa, fl 2 department of oncological sciences, h. Hyaluronan in cancer biology enhanced edition on apple books. Role of hyaluronan metabolism in the initiation, invasion. 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. Garantziotis, journalinternational journal of cell biology, year2015, volume2015. A, box plots of hyaluronan ha in healthy volunteers, cancer free patients and lung cancer patients lc. Turley, in hyaluronan in cancer biology, 2009 rhamm is a gene that belongs to a multifunctional group of cytoplasmic proteins, which are unconventionally exported to the cell surface in response to specific stimuli. 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. The ha is daily catabolized by the hyaluronidase enzymes to either oligosaccharides or larger polymer. Pdf highmolecularmass hyaluronan mediates the cancer.
Once again in the spotlight norihiro sato, 1shiro kohi, keiji hirata1 and michael goggins2 1department of surgery 1, school of medicine, university of occupational and environmental health, kitakyushu, japan. Hyaluronan in cancer biology ebook by 9780080921082. Certain hyaluronidases, products of tumor suppressor genes eliminated in the course of tumor spread. Hyaluronic acid targeting of cd44 for cancer therapy. Interactions of hyaluronan with cd44 in tumor cells play important cooperative roles in various aspects of malignancy and drug resistance. The role of extracellular matrix macromolecules in cancer. The faseb journal research communication a novel role of low molecular weight hyaluronan in breast cancer metastasis man wu,1 manlin cao,1 yiqing he, yiwen liu, cuixia yang, yan du, wenjuan wang, and feng gao,2 department of molecular biology, department of rehabilitation medicine, and department of molecular biology and clinical laboratory, shanghai jiao tong. High hyaluronan levels are associated with many human cancers. Hyaluronan stimulates pancreatic cancer cell motility oncotarget.
Cancer research hyaluronan deficiency in tumor stroma impairs. The discovery of hyaluronan synthase has genes, which encode the key enzymes in hyaluronan biosynthesis, has enabled great strides in understanding the mechanism underlying altered hyaluronan production in cancer and the involvement of this. Regulation of cancer cell functions by hyaluronan ha. Jan 01, 2009 hyaluronan ha is a sugarchain macromolecule in which nacetylglucosamine and glucuronic acid are linked together by alternating. Newly synthesized ha molecules are extruded directly onto the cell surface for assembly into. Hyaluronan is a linear glycosaminoglycan that consists of repeating disaccharide subunits of glucuronic acid and n. Levels of ha on the surface of tumor cells are indicators of poor outcome. During cancer progression, hyaluronan assembles an extracellular matrix that is favorable for both the motility and proliferation of cancer cells and the recruitment of inflammatory and bone marrow.
The most prominent biological and pathological feature that. Regulation of multidrug resistance in cancer cells by hyaluronan. For its critical biological functions the amount of ha in tissues is. Pdf hyaluronan has turned out to be an active regulator of cell behavior rather than solely an inert extracellular matrix component. Dissecting the role of hyaluronan synthases in the. Another concerning fact about lc is the mortality rate, which is responsible for 75. Hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor neovascularization nobutaka kobayashi 1,2, seiji miyoshi1, takahide mikami1, hiroshi koyama, masato kitazawa, michiko takeoka1, kenji sano3, jun amano2, zenzo isogai4, shumpei niida5, kayoko oguri6. A novel role of low molecular weight hyaluronan in breast. Pdf the role of hyaluronan in pancreatic cancer biology. Inhibition of tumor growth in vivo by hyaluronan oligomers. Since the discovery that the receptor is overexpressed in a variety of solid tumors, such as pancreatic, breast and lung c. In mammals ha is synthesised by three homologues ha synthases.
This observation was made in vivo using visible skin tumors, and would be attractive for the control of tumors such as malignant melanoma zeng et al. Anomalously, hyaluronan oligomers can inhibit tumor growth an anomaly of ha cancer biology is that ha oligomers injected into cancer sites markedly inhibit tumor growth. Vaidya and max myakishevrempel and julia ablaeva and z. A hallmark of tissue injury and repair is the turnover of extracellular matrix components. In addition to increased hyal2 expression, bladder cancer tissue is. The role of extracellular matrix macromolecules in cancer and. Paradoxically, both hyaluronan ha and hyaluronidases, the enzymes that eliminate ha, have also been correlated with cancer progression. May 14, 2015 the hyaluronan ha polymer is a critical component of extracellular matrix with a remarkable structure.
Pdf pancreatic ductal adenocarcinoma pdac remains the most deadly disease worldwide, with the lowest survival rate among all cancer. Dissecting the role of hyaluronan synthases in the tumor. Paradoxically, both hyaluronan ha and hyaluronidases. In several types of cancer cells, binding of hyaluronan to cd44 results in direct or indirect interaction of cd44 with signaling receptors, such as erbb2, epidermal growth factor receptor egfr, and transforming growth factor. Pdf the role of hyaluronan in pancreatic cancer biology and. Karamanos, advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan cd44 interactions and signaling in cancer, hyaluronan signaling and turnover, 10. Hyaluronan,cd44,andemmprinregulatelactateeffluxand. In cancer, decorin is considered to play a tumor suppressive role.
Binding of ha to cd44 has been shown to activate mapk, rac, and phosphoinositide 3. Hyaluronan ha, hyaluronic acid is a glycosaminoglycan gag polymer that is a major component of the extracellular matrix ecm 1, 2. Hyaluronan is a megadalton glycosaminoglycan polymer critical for maintaining the integrity of the extracellular matrix. Role of hyaluronan in pancreatic cancer biology and. A guide to hyaluronan and related enzymes in breast. Hyaluronan ha has long been recognized as essential to cancer biology. Bourguignon describes the characterization of microrna expression induced by hyaluronan of different sizes in cancer stem cells and suggests that specific microrna induction promotes cancer stem cell selfrenewal upon exposure to high molecular mass hyaluronan.
This chapter aims to bring attention to the field of ha and its role in cancer initiation, progression, and spread. Association between cancer and acid mucopolysaccharides introduction the influence of hyaluronan ha on cancer progression has been exceedingly well described toole, 2002. Hyaluronancell interactions in cancer and vascular. Microenvironmental stimuli can influence the malignant phenotype of cancer cells. Hyaluronan in cancer biology, first edition 3 10 11 o 2009 elsevier inc.
The physicochemical properties of ha are viscosity, elasticity, lubrication and a high capacity for holding water. Request pdf hyaluronan in cancer biology hyaluronan biology is being recognized as an important regulator of cancer progression. It is ubiquitous in mammals showing several biological functions, ranging from cell proliferation and migration to angiogenesis and inflammation. Cancer development has long been depicted as a progression of serial genetic mutations in a tumor cell mass.
Paradoxically, both hyaluronan ha and hyaluronidases, the enzymes that eliminate ha, can correlate with cancer progression. Hyaluronan ha is a ubiquitous constituent of extracellular matrices and has two main characteristics. Accumulation of ha in cancer cells, the cancersurrounding stroma, and ecm is generally considered. Despite its simple structure, ha is involved in a great number of biological functions, such as cell proliferation and. Other articles in this series concentrate on normal physiological and cellular functions of hyaluronan. Aug 21, 2008 hyaluronan acts as a microenvironmental stimulus that can influence the malignant phenotype of cancer cells. 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. Notably, the altered biosynthesis of hyaluronan, a constituent of the extracellular microenvironment, has been implicated in the progress and metastasis of carcinomas. The journal focuses on major new findings in the anatomical consequences of gene disruption, activation, or over expression upon cell. Identification of hyal2expressing tumorassociated myeloid cells in.
Both the synthesis and degradation of extracellular matrix are critical contributors to tissue repair and remodeling. Patients with lung cancer had significantly higher ha levels in sputum than in the cancer free patients and healthy volunteers log10 scale. The biological activities of this polysaccharide depend on its molecular weight and the identity of interacting receptors. Ha is implicated in a number of cell biological phenomena via ha receptors, cd44 and rhamm including cell. Cd44 in malignant growth, few studies exist on the presence of ha, its major ligand, on. It is unique among glycosaminoglycans as it is nonsulfated, forms in the plasma membrane instead of the golgi apparatus, and can be very large. Microenvironment and immunology hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor neovascularization nobutaka kobayashi 1,2, seiji miyoshi1, takahide mikami1, hiroshi koyama, masato kitazawa, michiko takeoka1, kenji sano3, jun amano2, zenzo isogai4, shumpei niida5, kayoko oguri6, minoru okayama7, john a.
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