Abstract
In an attempt to obtain inhibitors of hyaluronic acid (HA) binding to its receptor, CD44, we established an efficient assay method to detect and quantify binding using fluorescein-labeled HA and HEK293 cells stably expressing CD44. As a result of the screening of culture broths of microorganisms, we found fungus strain Gloeoporus dichrous SANK 30502 produced inhibitory activity in this new assay. Five compounds, F-16438 A, B, E, F and G, were isolated from the fermentation broths, and their IC50 values were determined to be 10.3, 13.5, 27.3, 12.0 and 13.0 μM, respectively. F-16438 A, B, E, F and G are the first reported inhibitors of binding HA to CD44. F-16438 A, B, E and F have novel structures.
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Toole BP . Proteoglycans and hyaluronan in morphogenesis and differentiation. In: Hay ED (ed). Cell Biology of Extracellular Matrix. Plenum Press, New York, pp. 61–92 ( 1991)
Toole BP . Hyaluronan in morphogenesis. Semin Cell Dev Biol 12: 79–87 ( 2001)
Longaker MT, Chiu ES, Adzick NS, Stern M, Harrison MR, Stern R . Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid. Ann Surg 213: 292–296 ( 1991)
Weigel PH, Fuller GM, LeBoeuf RD . A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing. J Theor Biol 119: 219–234 ( 1986)
de la Motte CA, Hascall VC, Drazba J, Bandyopadhyay SK . Strong SA. Mononuclear leukocytes bind to specific hyaluronan structures on colon mucosal smooth muscle cells treated with polyinosinic acid: polycytidylic acid: inter-alpha-trypsin inhibitor is crucial to structure and function. Am J Pathol 163: 121–133 ( 2003)
Majors AK, Austin RC, de la Motte CA, Pyeritz RE, Hascall VC, Kessler SP, Sen G, Strong SA . Endoplasmic reticulum stress induces hyaluronan deposition and leukocyte adhesion. J Biol Chem 278: 47223–47231 ( 2003)
Toole BP . Hyaluronan promotes the malignant phenotype. Glycobiology 12: 37–42 ( 2002)
Toole BP, Hascall VC . Hyaluronan and tumor growth. Am J Pathol 161: 745–747 ( 2002)
Ascher B, Cerceau M, Baspeyras M, Rossi B . Soft tissue filling with hyaluronic acid. Ann Chir Plast Esthet 49: 465–485 ( 2004)
Abatangelo G, O’Regan M . Hyaluronan: biological role and function in articular joints. Eur J Rheumatol Inflamm 15: 9–16 ( 1995)
Dahl LB, Dahl IMS, Engström-Laurent A, Granath K . Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 44: 817–822 ( 1985)
Ghosh P . The role of hyaluronic acid (hyaluronan) in health and disease: interactions with cells, cartilage and components of the synovial fluid. Clin Exp Rheumatol 12: 75–82 ( 1994)
Lesley J, Hyman R, Kincade PW . CD44 and its interaction with extracellular matrix. Adv Immunol 54: 271–335 ( 1993)
Picker LJ, Nakache M, Butcher EC . Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol 109: 927–937 ( 1989)
Bourguignon LY, Lokeshwar VB, He J, Chen X, Bourguignon GJ . A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin. Mol Cell Biol 12: 4464–4471 ( 1992)
Zhu D, Bourguignon LY . Overexpression of CD44 in pl85(neu)-transfected NIH3T3 cells promotes an up-regulation of hyaluronic acid-mediated membrane-cytoskeleton interaction and cell adhesion. Oncogene 12: 2309–2314 ( 1996)
Brown TA, Bouchard T, St John T, Wayner E, Carter WG . Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons. J Cell Biol 113: 207–221 ( 1991)
Grover J, Roughley PJ . Expression of cell-surface proteoglycan mRNA by human articular chondrocytes. Biochem J 309: 963–968 ( 1995)
Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B . CD44 is the principal cell surface receptor for hyaluronate. Cell 61: 1303–1313 ( 1990)
Miyake K, Underhill CB, Lesley J, Kincade PW . Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med 172: 69–75 ( 1990)
Stamenkovic I, Aruffo A, Amiot M, Seed B . The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate bearing cells. EMBO J 10: 343–348 ( 1991)
Shimizu Y, Van Seventer GA, Siraganian R, Wahl L, Shaw S . Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol 143: 2457–2463 ( 1989)
Lesley J, Howes N, Perschl A, Hyman R . Hyaluronan binding function of CD44 is transiently activated on T cells during an in vivo immune response. J Exp Med 180: 383–387 ( 1994)
Gunthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussmann I, Matzku S, Wenzel A, Ponta H, Herrlich P . A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 65: 13–24 ( 1991)
Sy MS, Guo YJ, Stamenkovic I . Distinct effects of two CD44 isoforms on tumor growth in vivo. J Exp Med 174: 859–866 ( 1991)
Udabage L, Brownlee GR, Nilsson SK, Brown TJ . The over-expression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer. Exp Cell Res 310: 205–217 ( 2005)
Chow G, Knudson CB, Homandberg G, Knudson W . Increased expression of CD44 in bovine articular chondrocytes by catabolic cellular mediators. J Biol Chem 270: 27734–27741 ( 1995)
Culty M, Nguyen HA, Underhill CB . The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan. J Cell Biol 116: 1055–1062 ( 1992)
Hua Q, Knudson CB, Knudson W . Internalization of hyaluronan by chondrocytes occurs via receptor-mediated endocytosis. J Cell Sci 106: 365–375 ( 1993)
Tammi R, Rilla K, Pienimaki JP, MacCallum DK, Hogg M, Luukkonen M, Hascall VC, Tammi M . Hyaluronan enters keratinocytes by a novel endocytic route for catabolism. J Biol Chem 276: 35111–35122 ( 2001)
Hirota-Takahara Y, Harada H, Tanaka I, Nakata T, Nakajima M, Takahashi M . F-16438s, novel binding inhibitors of and hyaluronic acid CD44. II. Producing organism, fermentation, isolation, physico-chemical properties and structural elucidation. J Antibiot 59: 770–776
de Belder AN, Wik KO . Preparation and properties of fluorescein-labelled hyaluronate. Carbohydr Res 44: 251–257 ( 1975)
Underhill CB, Toole BP . Physical characteristics of hyaluronate binding to the surface of simian virus 40-transformed 3T3 cells. J Biol Chem 255: 4544–4549 ( 1980)
Underhill CB, Green SJ, Comoglio PM, Tarone G . The hyaluronate receptor is identical to a glycoprotein of Mr 85,000 (gp85) as shown by a monoclonal antibody that interferes with binding activity. J Biol Chem 262: 13142–13146 ( 1987)
Underhill CB, Chi-Rosso G, Toole BP . Effects of detergent solubilization on the hyaluronate-binding protein from membranes of simian virus 40-transformed 3T3 cells. J Biol Chem 258: 8086–8091 ( 1983)
Weber W, Schu P, Anke T, Velten R, Steglich W . Caloporoside, a new inhibitor of phospholipases C from Caloporus dichrous (Fr.) Ryv. J Antibiot 47: 1188–1194 ( 1994)
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Harada, H., Nakata, T., Hirota-takahata, Y. et al. F-16438s, Novel Binding Inhibitors of CD44 and Hyaluronic Acid. J Antibiot 59, 770–776 (2006). https://doi.org/10.1038/ja.2006.101
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DOI: https://doi.org/10.1038/ja.2006.101
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