HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1

BMC Biochemistry - Tập 7 Số 1 - 2006
Kenji Uchimura1, Megumi Morimoto‐Tomita1, Annette Bistrup2, Jessica Li1, Malcolm Lyon3, John T. Gallagher3, Shingo Kajimura1, Steven D. Rosen1
1Department of Anatomy and the UCSF Comprehensive Cancer Center, University of California, San Francisco, USA
2Thios Pharmaceuticals, Emeryville, USA
3Department of Medical Oncology, University of Manchester, Paterson Institute for Cancer Research, Manchester, UK

Tóm tắt

Abstract Background Heparin/heparan sulfate (HS) proteoglycans are found in the extracellular matrix (ECM) and on the cell surface. A considerable body of evidence has established that heparin and heparan sulfate proteoglycans (HSPGs) interact with numerous protein ligands including fibroblast growth factors, vascular endothelial growth factor (VEGF), cytokines, and chemokines. These interactions are highly dependent upon the pattern of sulfation modifications within the glycosaminoglycan chains. We previously cloned a cDNA encoding a novel human endosulfatase, HSulf-2, which removes 6-O-sulfate groups on glucosamine from subregions of intact heparin. Here, we have employed both recombinant HSulf-2 and the native enzyme from conditioned medium of the MCF-7-breast carcinoma cell line. To determine whether HSulf-2 modulates the interactions between heparin-binding factors and heparin, we developed an ELISA, in which soluble factors were allowed to bind to immobilized heparin. Results Our results show that the binding of VEGF, FGF-1, and certain chemokines (SDF-1 and SLC) to immobilized heparin was abolished or greatly diminished by pre-treating the heparin with HSulf-2. Furthermore, HSulf-2 released these soluble proteins from their association with heparin. Native Sulf-2 from MCF-7 cells reproduced all of these activities. Conclusion Our results validate Sulf-2 as a new tool for deciphering the sulfation requirements in the interaction of protein ligands with heparin/HSPGs and expand the range of potential biological activities of this enzyme.

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Tài liệu tham khảo

Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, Lincecum J, Zako M: Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999, 68: 729-777. 10.1146/annurev.biochem.68.1.729.

Esko JD, Lindahl U: Molecular diversity of heparan sulfate. J Clin Invest. 2001, 108: 169-173. 10.1172/JCI200113530.

Ornitz DM: FGFs, heparan sulfate and FGFRs: complex interactions essential for development. Bioessays. 2000, 22: 108-112. 10.1002/(SICI)1521-1878(200002)22:2<108::AID-BIES2>3.0.CO;2-M.

Nakato H, Kimata K: Heparan sulfate fine structure and specificity of proteoglycan functions. Biochim Biophys Acta. 2002, 1573: 312-318.

Esko JD, Selleck SB: Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem. 2002, 71: 435-471. 10.1146/annurev.biochem.71.110601.135458.

Witt DP, Lander AD: Differential binding of chemokines to glycosaminoglycan subpopulations. Curr Biol. 1994, 4: 394-400. 10.1016/S0960-9822(00)00088-9.

Gallagher JT: Heparan sulfate: growth control with a restricted sequence menu. J Clin Invest. 2001, 108: 357-361. 10.1172/JCI200113713.

Lindahl U, Kusche-Gullberg M, Kjellen L: Regulated diversity of heparan sulfate. J Biol Chem. 1998, 273: 24979-24982. 10.1074/jbc.273.39.24979.

Powell AK, Yates EA, Fernig DG, Turnbull JE: Interactions of heparin/heparan sulfate with proteins: appraisal of structural factors and experimental approaches. Glycobiology. 2004, 14: 17R-30R. 10.1093/glycob/cwh051.

Murphy KJ, Merry CL, Lyon M, Thompson JE, Roberts IS, Gallagher JT: A new model for the domain structure of heparan sulfate based on the novel specificity of K5 lyase. J Biol Chem. 2004, 279: 27239-27245. 10.1074/jbc.M401774200.

Jayson GC, Vives C, Paraskeva C, Schofield K, Coutts J, Fleetwood A, Gallagher JT: Coordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma. Int J Cancer. 1999, 82: 298-304. 10.1002/(SICI)1097-0215(19990719)82:2<298::AID-IJC23>3.0.CO;2-9.

Brickman YG, Ford MD, Gallagher JT, Nurcombe V, Bartlett PF, Turnbull JE: Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development. J Biol Chem. 1998, 273: 4350-4359. 10.1074/jbc.273.8.4350.

Habuchi O: Diversity and functions of glycosaminoglycan sulfotransferases. Biochim Biophys Acta. 2000, 1474: 115-127.

Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CPJ: Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science. 2001, 293: 1663-1666. 10.1126/science.293.5535.1663.

Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD: Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem. 2002, 277: 49175-49185. 10.1074/jbc.M205131200.

Ai X, Do AT, Lozynska O, Kusche-Gullberg M, Lindahl U, Emerson CPJ: QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol. 2003, 162: 341-351. 10.1083/jcb.200212083.

Viviano BL, Paine-Saunders S, Gasiunas N, Gallagher J, Saunders S: Domain-specific modification of heparan sulfate by Qsulf1 modulates the binding of the bone morphogenetic protein antagonist Noggin. J Biol Chem. 2004, 279: 5604-5611. 10.1074/jbc.M310691200.

Ohto T, Uchida H, Yamazaki H, Keino-Masu K, Matsui A, Masu M: Identification of a novel nonlysosomal sulphatase expressed in the floor plate, choroid plexus and cartilage. Genes Cells. 2002, 7: 173-185. 10.1046/j.1356-9597.2001.00502.x.

Lai J, Chien J, Staub J, Avula R, Greene EL, Matthews TA, Smith DI, Kaufmann SH, Roberts LR, Shridhar V: Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer. J Biol Chem. 2003, 278: 23107-23117. 10.1074/jbc.M302203200.

Lai JP, Chien JR, Moser DR, Staub JK, Aderca I, Montoya DP, Matthews TA, Nagorney DM, Cunningham JM, Smith DI, Greene EL, Shridhar V, Roberts LR: hSulf1 Sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling. Gastroenterology. 2004, 126: 231-248. 10.1053/j.gastro.2003.09.043.

Lai JP, Chien J, Strome SE, Staub J, Montoya DP, Greene EL, Smith DI, Roberts LR, Shridhar V: HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma. Oncogene. 2004, 23: 1439-1447. 10.1038/sj.onc.1207258.

Wang S, Ai X, Freeman SD, Pownall ME, Lu Q, Kessler DS, Emerson CPJ: QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. Proc Natl Acad Sci U S A. 2004, 101: 4833-4838. 10.1073/pnas.0401028101.

Li J, Kleeff J, Abiatari I, Kayed H, Giese N, Felix K, Giese T, Buchler MW, Friess H: Enhanced levels of Hsulf-1 interfere with heparin-binding growth factor signaling in pancreatic cancer. Mol Cancer. 2005, 4: 14-10.1186/1476-4598-4-14.

Morimoto-Tomita M, Uchimura K, Rosen SD: Novel Extracellular Sulfatase: Potential Roles in Cancer. Trends in Glycoscience and Glycotechnology. 2003, 15: 159-164.

Morimoto-Tomita M, Uchimura K, Bistrup A, Lum DH, Egeblad M, Boudreau N, Werb Z, Rosen SD: Sulf-2, a proangiogenic heparan sulfate endosulfatase, is upregulated in breast cancer. Neoplasia. 2005, 7: 1001-1010. 10.1593/neo.05496.

Kamimura K, Fujise M, Villa F, Izumi S, Habuchi H, Kimata K, Nakato H: Drosophila heparan sulfate 6-O-sulfotransferase (dHS6ST) gene. Structure, expression, and function in the formation of the tracheal system. J Biol Chem. 2001, 276: 17014-17021. 10.1074/jbc.M011354200.

Bink RJ, Habuchi H, Lele Z, Dolk E, Joore J, Rauch GJ, Geisler R, Wilson SW, den Hertog J, Kimata K, Zivkovic D: Heparan sulfate 6-o-sulfotransferase is essential for muscle development in zebrafish. J Biol Chem. 2003, 278: 31118-31127. 10.1074/jbc.M213124200.

Kreuger J, Salmivirta M, Sturiale L, Gimenez-Gallego G, Lindahl U: Sequence analysis of heparan sulfate epitopes with graded affinities for fibroblast growth factors 1 and 2. J Biol Chem. 2001, 276: 30744-30752. 10.1074/jbc.M102628200.

Ashikari-Hada S, Habuchi H, Kariya Y, Itoh N, Reddi AH, Kimata K: Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccharide library. J Biol Chem. 2004, 279: 12346-12354. 10.1074/jbc.M313523200.

Feyzi E, Lustig F, Fager G, Spillmann D, Lindahl U, Salmivirta M: Characterization of heparin and heparan sulfate domains binding to the long splice variant of platelet-derived growth factor A chain. J Biol Chem. 1997, 272: 5518-5524. 10.1074/jbc.272.40.24850.

Ono K, Hattori H, Takeshita S, Kurita A, Ishihara M: Structural features in heparin that interact with VEGF165 and modulate its biological activity. Glycobiology. 1999, 9: 705-711. 10.1093/glycob/9.7.705.

Lyon M, Deakin JA, Mizuno K, Nakamura T, Gallagher JT: Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants. J Biol Chem. 1994, 269: 11216-11223.

Parthasarathy N, Goldberg IJ, Sivaram P, Mulloy B, Flory DM, Wagner WD: Oligosaccharide sequences of endothelial cell surface heparan sulfate proteoglycan with affinity for lipoprotein lipase. J Biol Chem. 1994, 269: 22391-22396.

Feyzi E, Trybala E, Bergstrom T, Lindahl U, Spillmann D: Structural requirement of heparan sulfate for interaction with herpes simplex virus type 1 virions and isolated glycoprotein C. J Biol Chem. 1997, 272: 24850-24857. 10.1074/jbc.272.40.24850.

Wang L, Brown JR, Varki A, Esko JD: Heparin's anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins. J Clin Invest. 2002, 110: 127-136. 10.1172/JCI200214996.

Ishihara M: Structural requirements in heparin for binding and activation of FGF-1 and FGF-4 are different from that for FGF-2. Glycobiology. 1994, 4: 817-824.

Turnbull JE, Fernig DG, Ke Y, Wilkinson MC, Gallagher JT: Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. J Biol Chem. 1992, 267: 10337-10341.

Saad OM, Ebel H, Uchimura K, Rosen SD, Bertozzi CR, Leary JA: Compositional profiling of heparin/heparan sulfate using mass spectrometry: assay for specificity of a novel extracellular human endosulfatase. Glycobiology. 2005, 15: 818-826. 10.1093/glycob/cwi064.

Pye DA, Vives RR, Turnbull JE, Hyde P, Gallagher JT: Heparan sulfate oligosaccharides require 6-O-sulfation for promotion of basic fibroblast growth factor mitogenic activity. J Biol Chem. 1998, 273: 22936-22942. 10.1074/jbc.273.36.22936.

Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N: Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem. 1992, 267: 26031-26037.

Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA: A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med. 1996, 184: 1101-1109. 10.1084/jem.184.3.1101.

Kucia M, Jankowski K, Reca R, Wysoczynski M, Bandura L, Allendorf DJ, Zhang J, Ratajczak J, Ratajczak MZ: CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol. 2004, 35: 233-245. 10.1023/B:HIJO.0000032355.66152.b8.

Christopherson KW, Hood AF, Travers JB, Ramsey H, Hromas RA: Endothelial induction of the T-cell chemokine CCL21 in T-cell autoimmune diseases. Blood. 2003, 101: 801-806. 10.1182/blood-2002-05-1586.

Elkin M, Ilan N, Ishai-Michaeli R, Friedmann Y, Papo O, Pecker I, Vlodavsky I: Heparanase as mediator of angiogenesis: mode of action. Faseb J. 2001, 15: 1661-1663.

Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D: Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000, 2: 737-744. 10.1038/35036374.

Vlodavsky I, Friedmann Y: Molecular properties and involvement of heparanase in cancer metastasis and angiogenesis. J Clin Invest. 2001, 108: 341-347. 10.1172/JCI200113662.

Goldshmidt O, Zcharia E, Abramovitch R, Metzger S, Aingorn H, Friedmann Y, Schirrmacher V, Mitrani E, Vlodavsky I: Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis. Proc Natl Acad Sci U S A. 2002, 99: 10031-10036. 10.1073/pnas.152070599.

Najjam S, Gibbs RV, Gordon MY, Rider CC: Characterization of human recombinant interleukin 2 binding to heparin and heparan sulfate using an ELISA approach. Cytokine. 1997, 9: 1013-1022. 10.1006/cyto.1997.0246.

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BMC Biochemistry

Tập 7 Số 1

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