Proteoglycans in health and disease: Novel roles for proteoglycans in malignancy and their pharmacological targeting

FEBS Journal

Volumn 277, Issue 19, 2010, Pages 3904-3923

  Theocharis, Achilleas D ^a   Skandalis, Spyridon S ^b   Tzanakakis, George N ^c   Karamanos, Nikos K ^a  

^a UNIVERSITY OF PATRAS   (Greece)

^b LUDWIG INSTITUTE FOR CANCER RESEARCH   (Sweden)

^c UNIVERSITY OF CRETE   (Greece)

Author keywords

cancer; decorin; glypicans; lumican; molecular targeting; perlecan; proteoglycans; serglycin; syndecans; versican

Indexed keywords

PERLECAN; PROTEINASE; PROTEOGLYCAN; SYNDECAN; VERSICAN; AGGRECAN; AGRIN; BCAN PROTEIN, HUMAN; BIOLOGICAL MARKER; BREVICAN; DCN PROTEIN, HUMAN; DECORIN; HYALURONIC ACID; LECTIN; NERVE PROTEIN; PROTEOCHONDROITIN SULFATE; SCLEROPROTEIN;

ANGIOGENESIS; CANCER CELL; CANCER GROWTH; CANCER THERAPY; CARCINOGENESIS; CELL ADHESION; CELL COMMUNICATION; CELL PROLIFERATION; CELL SURFACE; CELL SURVIVAL; DISEASE ASSOCIATION; DRUG TARGETING; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; HEALTH; HUMAN; MALIGNANT NEOPLASTIC DISEASE; MALIGNANT TRANSFORMATION; METABOLIC REGULATION; NONHUMAN; PRIORITY JOURNAL; PROTEOGLYCAN SYNTHESIS; SHORT SURVEY; SOLID TUMOR; STROMA CELL; TISSUE SPECIFICITY; TUMOR GROWTH; CARTILAGE; CELL DIVISION; DISEASE COURSE; DRUG EFFECTS; GENETICS; GLIOMA; INFLAMMATION; METABOLISM; NEOPLASMS; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PROGNOSIS;

AGGRECANS; AGRIN; BIOLOGICAL MARKERS; BREVICAN; CARTILAGE; CELL DIVISION; CHONDROITIN SULFATE PROTEOGLYCANS; DECORIN; DISEASE PROGRESSION; EXTRACELLULAR MATRIX PROTEINS; GLIOMA; HUMANS; HYALURONIC ACID; INFLAMMATION; LECTINS, C-TYPE; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; NERVE TISSUE PROTEINS; PROGNOSIS; PROTEOGLYCANS; VERSICANS;

EID: 77956641177     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/j.1742-4658.2010.07800.x     Document Type: Short Survey

References (157)

1. Iozzo RV (1998) Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem 67, 609 652.
2. Schaefer L Schaefer RM (2010) Proteoglycans: from structural compounds to signaling molecules. Cell Tissue Res 339, 237 246.
3. Syrokou A, Tzanakakis G, Tsegenidis T, Hjerpe A Karamanos NK (1999) Effects of glycosaminoglycans on proliferation of epithelial and fibroblast human malignant mesothelioma cells: a structure-function relationship. Cell Prolif 32, 85 99.
4. Wight TN (2002) Versican: a versatile extracellular matrix proteoglycan in cell biology. Curr Opin Cell Biol 14, 617 623.
5. Wight TN Merrilees MJ (2004) Proteoglycans in atherosclerosis and restenosis: key roles for versican. Circ Res 94, 1158 1167.
6. Theocharis AD (2008) Versican in health and disease. Connect Tissue Res 49, 230 234.
7. Wu YJ, Lapierre D, Wu J, Yee AJ Yang BB (2005) The interaction of versican with its binding partners. Cell Res 15, 483 494.
8. Kim S, Takahashi H, Lin WW, Descargues P, Grivennikov S, Kim Y, Luo JL Karin M (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457, 102 106.
9. Sakko AJ, Ricciardelli C, Mayne K, Tilley WD, LeBaron RG Horsfall DJ (2001) Versican accumulation in human prostatic fibroblast cultures is enhanced by prostate cancer cell-derived transforming growth factor beta1. Cancer Res 61, 926 930.
10. Ricciardelli C, Brooks JH, Suwiwat S, Sakko AJ, Mayne K, Raymond WA, Seshadri R, LeBaron RG Horsfall DJ (2002) Regulation of stromal versican expression by breast cancer cells and importance to relapse-free survival in patients with node-negative primary breast cancer. Clin Cancer Res 8, 1054 1060.
11. Nikitovic D, Zafiropoulos A, Katonis P, Tsatsakis A, Theocharis AD, Karamanos NK Tzanakakis GN (2006) Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells. IUBMB Life 58, 47 53.
12. Arslan F, Bosserhoff AK, Nickl-Jockschat T, Doerfelt A, Bogdahn U Hau P (2007) The role of versican isoforms V0/V1 in glioma migration mediated by transforming growth factor-beta2. Br J Cancer 96, 1560 1568.
13. Serra M, Miquel L, Domenzain C, Docampo MJ, Fabra A, Wight TN Bassols A (2005) V3 versican isoform expression alters the phenotype of melanoma cells and their tumorigenic potential. Int J Cancer 114, 879 886.
14. Miquel-Serra L, Serra M, Hernández D, Domenzain C, Docampo MJ, Rabanal RM, de Torres I, Wight TN, Fabra A Bassols A (2006) V3 versican isoform expression has a dual role in human melanoma tumor growth and metastasis. Lab Invest 86, 889 901.
15. Ricciardelli C, Mayne K, Sykes PJ, Raymond WA, McCaul K, Marshall VR Horsfall DJ (1998) Elevated levels of versican but not decorin predict disease progression in early stage prostate cancer. Clin Cancer Res 4, 963 971.
16. Pirinen R, Leinonen T, Böhm J, Johansson R, Ropponen K, Kumpulainen E Kosma VM (2005) Versican in nonsmall cell lung cancer: relation to hyaluronan, clinicopathologic factors, and prognosis. Hum Pathol 36, 44 50.
17. Pukkila M, Kosunen A, Ropponen K, Virtaniemi J, Kellokoski J, Kumpulainen E, Pirinen R, Nuutinen J, Johansson R Kosma VM (2007) High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma. J Clin Pathol 60, 267 272.
18. Labropoulou VT, Theocharis AD, Ravazoula P, Perimenis P, Hjerpe A, Karamanos NK Kalofonos HP (2006) Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumors. Histopathology 49, 582 593.
19. Suwiwat S, Ricciardelli C, Tammi R, Tammi M, Auvinen P, Kosma VM, LeBaron RG, Raymond WA, Tilley WD Horsfall DJ (2004) Expression of extracellular matrix components versican, chondroitin sulfate, tenascin, and hyaluronan, and their association with disease outcome in node negative breast cancer. Clin Cancer Res 10, 2491 2498.
20. Kodama J, Hasengaowa, Kusumoto T, Seki N, Matsuo T, Nakamura K, Hongo A Hiramatsu Y (2007) Versican expression in human cervical cancer. Eur J Cancer 43, 1460 1466.
21. Kodama J, Hasengaowa, Kusumoto T, Seki N, Matsuo T, Ojima Y, Nakamura K, Hongo A Hiramatsu Y (2007) Prognostic significance of stromal versican expression in human endometrial cancer. Ann Oncol 18, 269 274. (Pubitemid 46323092)
22. Mauri P, Scarpa A, Nascimbeni AC, Benazzi L, Parmagnani E, Mafficini A, Della Peruta M, Bassi C, Miyazaki K Sorio C (2005) Identification of proteins released by pancreatic cancer cells by multidimensional protein identification technology: a strategy for identification of novel cancer markers. FASEB J 19, 1125 1127.
23. Cattaruzza S, Schiappacassi M, Kimata K, Colombatti A Perris R (2004) The globular domains of PGM/versican modulate the proliferation-apoptosis equilibrium and invasive capabilities of tumor cells. FASEB J 18, 779 781.
24. Zheng PS, Wen J, Ang LC, Sheng W, Viloria-Petit A, Wang Y, Wu Y, Kerbel RS Yang BB (2004) Versican/PG-M G3 domain promotes tumor growth and angiogenesis. FASEB J 18, 754 756.
25. Ricciardelli C, Russell DL, Ween MP, Mayne K, Suwiwat S, Byers S, Marshall VR, Tilley WD Horsfall DJ (2007) Formation of hyaluronan- and versican-rich pericellular matrix by prostate cancer cells promotes cell motility. J Biol Chem 282, 10814 10825.
26. LaPierre DP, Lee DY, Li SZ, Xie YZ, Zhong L, Sheng W, Deng Z Yang BB (2007) The ability of versican to simultaneously cause apoptotic resistance and sensitivity. Cancer Res 67, 4742 4750.
27. Yee AJ, Akens M, Yang BL, Finkelstein J, Zheng PS, Deng Z Yang B (2007) The effect of versican G3 domain on local breast cancer invasiveness and bony metastasis. Breast Cancer Res 9, R47.
28. Touab M, Villena J, Barranco C, Arumi-Uria M Bassols A (2002) Versican is differentially expressed in human melanoma and may play a role in tumor development. Am J Pathol 160, 549 557.
29. Sakko AJ, Ricciardelli C, Mayne K, Suwiwat S, LeBaron RG, Marshall VR, Tilley WD Horsfall DJ (2003) Modulation of prostate cancer cell attachment to matrix by versican. Cancer Res 63, 4786 4791.
30. Zhang Y, Cao L, Yang BL Yang BB (1998) The G3 domain of versican enhances cell proliferation via epidermal growth factor-like motifs. J Biol Chem 273, 21342 21351. (Pubitemid 28385428)
31. Yang BL, Zhang Y, Cao L Yang BB (1999) Cell adhesion and proliferation mediated through the G1 domain of versican. J Cell Biochem 72, 210 220. (Pubitemid 29021934)
32. Wang W, Xu G-L, Jia W-D, Ma J-L, Li J-S, Ge Y-S, Ren W-H, Yu J-H Liu W-B (2009) Ligation of TLR2 by versican: a link between inflammation and metastasis. Arch Med Res 40, 321 323.
33. Naso MF, Zimmermann DR Iozzo RV (1994) Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter. J Biol Chem 269, 32999 33008.
34. Yoon H, Liyanarachi S, Wright FA, Davuluri R, Lockman JC, Chapelle A Pellegata NS (2002) Gene expression profiling of isogenic cells with different TP53 gene dosage reveals numerous genes that are affected by TP53 dosage and identifies CSPG2 as a direct target of p53. Proc Natl Acad Sci USA 99, 15632 15637.
35. Willert J, Epping M, Pollack Jr. Brown PO Nusse R (2002) A transcriptional response to Wnt protein in human embryonic carcinoma cells. BMC Dev Biol 2, 8. doi: 10.1186/1471-213X-2-8.
36. Berdiaki A, Zafiropoulos A, Fthenou E, Katonis P, Tsatsakis A, Karamanos NK Tzanakakis GN (2008) Regulation of hyaluronan and versican deposition by growth factors in fibrosarcoma cell lines. Biochim Biophys Acta 1780, 194 202.
37. Syrokou A, Tzanakakis GN, Hjerpe A Karamanos NK (1999) Proteoglycans in human malignant mesothelioma. Stimulation of their synthesis induced by epidermal, insulin and platelet-derived growth factors involves receptors with tyrosine kinase activity. Biochimie 81, 733 744.
38. Shimizu-Hirota R, Sasamura H, Mifune M, Nakaya H, Kuroda M, Hayashi M Saruta T (2001) Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. J Am Soc Nephrol 12, 2609 2615.
39. * functions. PLoS ONE 4, e4527. doi:10.1371/journal. pone.0004527
40. Migliore C, Petrelli A, Ghiso E, Corso S, Capparuccia L, Eramo A, Comoglio PM Giordano S (2008) MicroRNAs impair MET-mediated invasive growth. Cancer Res 68, 10128 10136.
41. Seto AG (2010) The road toward microRNA therapeutics. Int J Biochem Cell Biol 42, 1298 1305.
42. Ricciardelli C, Sakko AJ, Ween MP, Russell DL Horsfall DJ (2009) The biological role and regulation of versican levels in cancer. Cancer Metastasis Rev 28, 233 245.
43. Almholt K, Juncker-Jensen A, Laerum OD, Danø K, Johnsen M, Lund LR Rømer J (2008) Metastasis is strongly reduced by the matrix metalloproteinase inhibitor Galardin in the MMTV-PymT transgenic breast cancer model. Mol Cancer Ther 7, 2758 2767.
44. Vankemmelbeke MN, Jones GC, Fowles C, Ilic MZ, Handley CJ, Day AJ, Knight CG, Mort JS Buttle DJ (2003) Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters. Eur J Biochem 270, 2394 2403.
45. Zeng C, Toole BP, Kinney SD, Kuo JW Stamenkovic I (1998) Inhibition of tumor growth in vivo by hyaluronan oligomers. Int J Cancer 77, 396 401.
46. Misra S, Toole BP Ghatak S (2006) Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells. J Biol Chem 281, 34936 34941.
47. Skandalis SS, Theocharis AD, Vynios DH, Papageorgakopoulou N, Hjerpe A, Karamanos NK Theocharis DA (2006) Cartilage aggrecan undergoes significant compositional and structural alterations during laryngeal cancer. Biochim Biophys Acta 1760, 1046 1055.
48. Skandalis SS, Theocharis AD, Theocharis DA, Papadas T, Vynios DH Papageorgakopoulou N (2004) Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma. Biochim Biophys Acta 1689, 152 161.
49. Nutt CL, Zerillo CA, Kelly GM Hockfield S (2001) Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats. Cancer Res 61, 7056 7059.
50. Hu B, Kong LL, Matthews RT Viapiano MS (2008) The proteoglycan brevican binds to fibronectin after proteolytic cleavage and promotes glioma cell motility. J Biol Chem 283, 24848 24859.
51. Viapiano MS, Bi WL, Piepmeier J, Hockfield S Matthews RT (2005) Novel tumor-specific isoforms of BEHAB/brevican identified in human malignant gliomas. Cancer Res 65, 6726 6733.
52. Schaefer L Iozzo RV (2008) Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem 283, 21305 21309.
53. Iozzo RV Schaefer L (2010) Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans. FEBS J 277, 3864 3875.
54. Iozzo RV, Chakrani F, Perrotti D, McQuillan DJ, Skorski T, Calabretta B Eichstetter I (1999) Cooperative action of germline mutations in decorin and p53 accelerates lymphoma tumorigenesis. Proc Natl Acad Sci USA 96, 3092 3097.
55. Csordas G, Santra M, Reed CC, Eichstetter I, McQuillan DJ, Gross D, Nugent MA, Hajnoczky G Iozzo RV (2000) Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem 275, 32879 32887.
56. Santra M, Mann DM, Mercer EW, Skorski T, Calabretta B Iozzo RV (1997) Ectopic expression of decorin protein core causes a generalized growth suppression in neoplastic cells of various histogenetic origin and requires endogenous p21, an inhibitor of cyclin-dependent kinases. J Clin Invest 100, 149 157.
57. Santra M, Eichstetter I Iozzo RV (2000) An anti-oncogenic role for decorin: downregulation of ErbB2 leads to growth suppression and cytodifferentiation of mammary carcinoma cells. J Biol Chem 275, 35153 35161.
58. Gialeli Ch, Kletsas D, Mavroudis D, Kalofonos HP, Tzanakakis GN Karamanos NK (2009) Targeting epidermal growth factor receptor in solid tumors: critical evaluation of the biological importance of therapeutic monoclonal antibodies. Curr Med Chem 16, 3797 3804.
59. Zhu J-X, Goldoni S, Bix G, Owens RA, McQuillan D, Reed CC Iozzo RV (2005) Decorin evokes protracted internalization and degradation of the EGF receptor via caveolar endocytosis. J Biol Chem 280, 32468 32479.
60. Reed CC, Waterhouse A, Kirby S, Kay P, Owens RA, McQuillan DJ Iozzo RV (2005) Decorin prevents metastatic spreading of breast cancer. Oncogene 24, 1104 1110.
61. Zafiropoulos A, Nikitovic D, Katonis P, Tsatsakis A, Karamanos NK Tzanakakis GN (2008) Decorin-induced growth inhibition is overcome through protracted expression and activation of epidermal growth factor receptors in osteosarcoma cells. Mol Cancer Res 6, 785 794.
62. Goldoni S, Humphries A, Nyström A, Sattar S, Owens RT, McQuillan DJ, Ireton K Iozzo RV (2009) Decorin is a novel antagonistic ligand of the Met receptor. J Cell Biol 185, 743 754.
63. Newton TR, Parsons PG, Lincoln DJ, Cummings MC, Wyld DK, Webb PM, Green AC Boyle GM (2006) Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer. Int J Cancer 119, 875 883.
64. Troup S, Njue C, Kliewer EV, Parisien M, Roskelley C, Chakravarti S, Roughley PJ, Murphy LC Watson PH (2003) Reduced expression of the small leucine-rich proteoglycans, lumican, and decorin is associated with poor outcome in node-negative invasive breast cancer. Clin Cancer Res 9, 207 214.
65. Matsumine A, Shintani K, Kusuzaki K, Matsubara T, Satonaka H, Wakabayashi T, Iino T Uchida A (2007) Expression of decorin, a small leucine-rich proteoglycan, as a prognostic factor in soft tissue tumors. J Surg Oncol 96, 411 418.
66. Theocharis AD (2002) Human colon adenocarcinoma is associated with specific post-translational modifications of versican and decorin. Biochim Biophys Acta 1588, 165 172.
67. Nash MA, Deavers MT Freedman RS (2002) The expression of decorin in human ovarian tumors. Clin Cancer Res 8, 1754 1760.
68. Theocharis AD, Vynios DH, Papageorgakopoulou N, Skandalis SS Theocharis DA (2003) The gastric carcinoma glycosaminoglycans and proteoglycans undergo marked alterations in their content, composition and chemical structure. Int J Biochem Cell Biol 35, 376 390.
69. Skandalis SS, Kletsas D, Kyriakopoulou D, Stavropoulos M Theocharis DA (2006) The greatly increased amounts of accumulated versican and decorin with specific post-translational modifications may be closely associated with the malignant phenotype of pancreatic cancer. Biochim Biophys Acta 1760, 1217 1225.
70. Köninger J, Giese T, di Mola FF, Wente MN, Esposito I, Bachem MG, Giese NA, Büchler MW Friess H (2004) Pancreatic tumor cells influence the composition of the extracellular matrix. Biochem Biophys Res Commun 322, 943 949.
71. Nash MA, Loercher AE Freedman RS (1999) In vitro growth inhibition of ovarian cancer cells by decorin: synergism of action between decorin and carboplatin. Cancer Res 59, 6192 6196.
72. Koninger J, Giese NA, di Mola FF, Berberat P, Giese T, Esposito I, Bachem MG, Buchler MW Friess H (2004) Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action. Clin Cancer Res 10, 4776 4783.
73. Tralhao JG, Schaefer L, Micegova M, Evaristo C, Schonherr E, Kayal S, Veiga-Fernandes H, Danel C, Iozzo RV, Kresse H et al. (2003) In vivo selective and distant killing of cancer cells using adenovirus mediated decorin gene transfer. FASEB J 17, 464 466.
74. Biglari A, Bataille D, Naumann U, Weller M, Zirger J, Castro MG Lowenstein PR (2004) Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther 11, 721 732.
75. Goldoni S Iozzo RV (2008) Tumor microenvironment: modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int J Cancer 123, 2473 2479.
76. Goldoni S, Seidler DG, Heath J, Fassan M, Baffa R, Thakur ML, Owens RA, McQuillan DJ Iozzo RV (2008) An anti-metastatic role for decorin in breast cancer. Am J Pathol 173, 844 855.
77. Li Y, Aoki T, Mori Y, Ahmad M, Miyamori H, Takino T Sato H (2004) Cleavage of lumican by membrane-type matrix metalloprotease-1 abrogates this proteoglycan-mediated suppression of tumor cell colony formation in soft agar. Cancer Res 64, 7058 7064.
78. Nikitovic D, Berdiaki A, Zafiropoulos A, Katonis P, Tsatsakis A, Karamanos N Tzanakakis GN (2008) Lumican expression is positively correlated with the differentiation and negatively with the growth of human osteosarcoma cells. FEBS J 275, 350 361.
79. Vuillermoz B, Khoruzhenko A, D'Onofrio MF, Ramont L, Venteo L, Perreau C, Antonicelli F, Maquart FX Wegrowski Y (2004) The small leucine-rich proteoglycan lumican inhibits melanoma progression. Exp Cell Res 296, 294 306.
80. Leygue E, Snell L, Dotzlaw H, Troup S, Hiller-Hitchcock T, Murphy LC, Roughley PJ Watson PH (2000) Lumican and decorin are differentially expressed in human breast carcinoma. J Pathol 192, 313 320.
81. Zeltz C, Brezillon S, Perreau C, Ramont L, Maquart F-X Wegrowski Y (2009) Lumcorin: a leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration. FEBS Lett 583, 3027 3032.
82. Iozzo RV, Zoeller JJ Nyström A (2009) Basement membrane proteoglycans: modulators par excellence of cancer growth and angiogenesis. Mol Cells 27, 503 513.
83. Zhou Z, Wang J, Cao R, Morita H, Soininen R, Chan KM, Liu B, Cao Y Tryggvason K (2004) Impaired angiogenesis, delayed wound healing and retarded tumor growth in perlecan heparan sulfate-deficient mice. Cancer Res 64, 4699 4702.
84. Sharma B, Handler M, Eichstetter I, Whitelock J, Nugent MA Iozzo RV (1998) Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo. J Clin Invest 102, 1599 1608.
85. Kadenhe-Chiweshe A, Papa J, McCrudden KW, Frischer J, Bae J-O, Huang J, Fisher J, Lefkowitch JH, Feirt N, Rudge J et al. (2008) Sustained VEGF blockade results in microenvironmental sequestration of VEGF by tumors and persistent VEGF receptor-2 activation. Mol Cancer Res 6, 1 9.
86. Reiland J, Sanderson RD, Waguespack M, Barker SA, Long R, Carson DD Marchetti D (2004) Heparanase degrades syndecan-1 and perlecan heparan sulfate: functional implications for tumor cell invasion. J Biol Chem 279, 8047 8055.
87. Whitelock JM, Murdoch AD, Iozzo RV Underwood PA (1996) The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin and heparanases. J Biol Chem 271, 10079 10086.
88. Bix G, Fu J, Gonzalez E, Macro L, Barker A, Campbell S, Zutter MM, Santoro SA, Kim JK, Höök M et al. (2004) Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through the α2β1 integrin. J Cell Biol 166, 97 109.
89. Nyström A, Shaik ZP, Gullberg D, Krieg T, Eckes B, Zent R, Pozzi A Iozzo RV (2009) Role of tyrosine phosphatase SHP-1 in the mechanism of endorepellin angiostatic activity. Blood 114, 4897 4906.
90. Bix G, Castello R, Burrows M, Zoeller JJ, Weech M, Iozzo RA, Cardi C, Thakur MT, Barker CA, Camphausen KC et al. (2006) Endorepellin in vivo: targeting the tumor vasculature and retarding cancer growth and metabolism. J Natl Cancer Inst 98, 1634 1646.
91. Gonzalez EM, Reed CC, Bix G, Fu J, Zhang Y, Gopalakrishnan B, Greenspan DS Iozzo RV (2005) BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan. J Biol Chem 280, 7080 7087.
92. Chang JW, Kang U-B, Kim DH, Yi JK, Lee JW, Noh D-Y, Lee C Yu M-H (2008) Identification of circulating endorepellin LG3 fragment: potential use as a serological biomarker for breast cancer. Proteomics Clin Appl 2, 23 32.
93. Ferreras M, Felbor U, Lenhard T, Olsen BR Delaisse J (2000) Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett 486, 247 251.
94. Sund M Kalluri R (2009) Tumor stroma derived biomarkers in cancer. Cancer Metastasis Rev 28, 177 183.
95. Sauter BV, Martinet O, Zhang W-J, Mandeli J Woo SLC (2001) Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastasis. Proc Natl Acad Sci USA 97, 4802 4807.
96. Abdollahi A, Hahnfeldt P, Maercker C, Gröne H-J, Debus J, Ansorge W, Folkman J, Hlatky L Huber PE (2004) Endostatin's antioangiogenic signaling network. Mol Cell 13, 649 663.
97. Kuo CJ, LaMontagne KR, Garcia-Cardena G, Ackley BD, Kalman D, Park S, Christofferson R, Kamihara J, Ding Y-H, Lo K-M et al. (2001) Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NC1/endostatin domain. J Cell Biol 152, 1233 1246.
98. Rodrigues DB, Chammas R, Malavasi NV, daCosta PLN, Chura-Chambi RM, Balduino KN Morganti L (2010) Anti-tumor therapy with macroencapsulated endostatin producer cells. BMC Biotechnol 10, 19.
99. Tátrai P, Dudás J, Batmunkh E, Máthé M, Zalatnai A, Schaff Z, Ramadori G Kovalszky I (2006) Agrin, a novel basement membrane component in human rat and liver, accumulates in cirrhosis and hepatocellular carcinoma. Lab Invest 86, 1149 1160.
100. Batmunkh E, Tátrai P, Szabó E, Lódi C, Holczbauer A, Páska C, Kupcsulik P, Kiss A, Schaff Z Kovalszky I (2007) Comparison of the expression of agrin, a basement membrane heparan sulfate proteoglycan, in cholangiocarcinoma and hepatocellular carcinoma. Hum Pathol 38, 1508 1515.
101. Filmus J, Capurro M Rast J (2008) Glypicans. Genome Biol 9, 224.
102. Capurro MI, Xu P, Shi W, Li F, Jia A Filmus J (2008) Glypican-3 inhibits hedgehog signaling during development by competing with Patched for Hedgehog binding. Dev Cell 14, 700 711.
103. Song HH, Shi W, Xiang Y Filmus J (2005) The loss of glypican-3 induces alterations in Wnt signaling. J Biol Chem 280, 2116 2125.
104. Kirkpatrick CA, Knox SM, Staatz WD, Fox B, Lercher DM Selleck SB (2006) The function of a Drosophila glypican does not depend entirely on heparan sulfate modification. Dev Biol 300, 570 582.
105. Kleeff J, Ishiwata T, Kumbasar A, Friess H, Buchler MW, Lander AD Korc M (1998) The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. J Clin Invest 102, 1662 1673.
106. Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD Korc M (2001) Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Res 61, 5562 5569.
107. Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A Schlessinger D (1996) Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet 12, 241 247.
108. Gonzalez AD, Kaya M, Shi W, Song H, Testa Jr. Penn LZ Filmus J (1998) OCI-5/GPC3, a glypican encoded by a gene that is mutated in the Simpson-Golabi-Behmel overgrowth syndrome, induces apoptosis in a cell line-specific manner. J Cell Biol 141, 1407 1414.
109. Kim H, Xu GL, Borczuk AC, Busch S, Filmus J, Capurro M, Brody JS, Lange J, D'Armiento JM, Rothman PB et al. (2003) The heparan sulfate proteoglycan GPC3 is a potential lung tumor suppressor. Am J Respir Cell Mol Biol 29, 694 701.
110. Zhu Z, Friess H, Kleeff J, Wang L, Wirtz M, Zimmermann A, Korc M Buchler MW (2002) Glypican-3 expression is markedly decreased in human gastric cancer but not in esophageal cancer. Am J Surg 184, 78 83.
111. Lin H, Huber R, Schlessinger D Morin PJ (1999) Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res 59, 807 810.
112. Murthy SS, Shen T, De Rienzo A, Lee WC, Ferriola PC, Jhanwar SC, Mossman BT, Filmus J Testa Jr. (2000) Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma. Oncogene 19, 410 416.
113. Yuan Z, Goetz JA, Singh S, Ogden SK, Petty SK, Black CC, Memoli VA, Dmitrovsky E Robbins DJ (2006) Frequent requirement of hedgehog signaling in non-small cell lung carcinoma. Oncogene 26, 1046 1055.
114. Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, Kuroki S Katano M (2004) Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 64, 6071 6074.
115. Saikali Z Sinnett D (2000) Expression of glypican 3 (GPC3) in embryonal tumors. Int J Cancer 89, 418 422.
116. Nakatsura T, Kageshita T, Ito S, Wakamatsu K, Monji M, Ikuta Y, Senju S, Ono T Nishimura Y (2004) Identification of glypican-3 as a novel tumor marker for melanoma. Clin Cancer Res 10, 6612 6621.
117. 2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res 64, 2418 2423.
118. Bloushtain N, Qimron U, Bar-Ilan A, Hershkovitz O, Gazit R, Fima E, Korc M, Vlodavsky I, Bovin NV Porgador A (2004) Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. J Immunol 173, 2392 2401.
119. Fears CY Woods A (2006) The role of syndecans in disease and wound healing. Matrix Biol 25, 443 456.
120. Manon-Jensen T, Itoh Y Couchman Jr. (2010) Proteoglycans in health and disease: the multiple roles of syndecan shedding. FEBS J 277, 3876 3889.
121. Chen D, Adenekan B, Chen L, Vaughan ED, Gerald W, Feng Z Knudsen BS (2004) Syndecan-1 expression in locally invasive and metastatic prostate cancer. Urology 63, 402 407.
122. Barbareschi M, Maisonneuve P, Aldovini D, Cangi MG, Pecciarini L, Mauri F, Veronese S, Caffo O, Lucenti A, Palma PD et al. (2003) High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer 98, 474 483.
123. Alexander CM, Reichsman F, Hinkes MT, Lincecum J, Becker KA, Cumberledge S Bernfield M (2000) Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice. Nat Genet 25, 329 332.
124. Beauvais DM Rapraeger AC (2003) Syndecan-1-mediated cell spreading requires signaling by alphavbeta3 integrins in human breast carcinoma cells. Exp Cell Res 286, 219 232.
125. Maeda T, Alexander CM Friedl A (2004) Induction of syndecan-1 expression in stromal fibroblasts promotes proliferation of human breast cancer cells. Cancer Res 64, 612 621.
126. Maeda T, Desouky J Friedl A (2006) Syndecan-1 expression by stromal fibroblasts promotes breast carcinoma growth in vivo and stimulates tumor angiogenesis. Oncogene 2, 1408 1412.
127. Chang Z, Meyer K, Rapraeger AC Friedl A (2000) Differential ability of heparan sulfate proteoglycans to assemble the fibroblast growth factor receptor complex in situ. FASEB J 14, 137 144.
128. Gospodarowicz D Cheng J (1986) Heparin protects basic and acidic FGF from inactivation. J Cell Physiol 128, 475 484.
129. Anttonen A, Heikkila P, Kajant IM, Jalkanen M Joensuu H (2001) High syndecan-1 expression is associated with favourable outcome in squamous cell lung carcinoma treated with radical surgery. Lung Cancer 32, 297 305.
130. Lundin M, Nordling S, Lundin J, Wiksten J-P Haglund C (2005) Epithelial syndecan-1 expression is associated with stage and grade in colorectal cancer. Oncology 68, 306 313.
131. Shinyo Y, Kodama J, Hasengaowa, Kusumoto T Hiramatsu Y (2005) Loss of cell-surface heparan sulfate expression in both cervical intraepithelial neoplasm and invasive cervical cancer. Gynecol Oncol 96, 776 783.
132. Juuti A, Nordling S, Lundin J, Louhimo J Haglund C (2005) Syndecan-1 expression - a novel prognostic marker in pancreatic cancer. Oncology 68, 97 106.
133. Leivonen M, Lundin J, Nordling S, von Boguslawski K Haglund C (2004) Prognostic value of syndecan-1 expression in breast cancer. Oncology 67, 11 18.
134. Mukunyadzi P, Liu K, Hanna EY, Suen JY Fan CY (2003) Induced expression of syndecan-1 in the stroma of head and neck squamous cell carcinoma. Mod Pathol 16, 796 801.
135. Wiksten JP, Lundin J, Nordling S, Lundin M, Kokkola A, von Boguslawski K Haglund C (2001) Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer. Int J Cancer 95, 1 6.
136. Ding K, Lopez-Burks M, Sánchez-Duran JA, Korc M Lander AD (2005) Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J Cell Biol 171, 729 738.
137. Fitzgerald ML, Wang Z, Park PW, Murphy G Bernfield M (2000) Shedding of syndecan-1 and -4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase. J Cell Biol 148, 811 824.
138. Wang Z, Gotte M, Bernfield M Reizes O (2005) Constitutive and accelerated shedding of murine syndecan-1 is mediated by cleavage of its core protein at a specific juxtamembrane site. Biochemistry 44, 12355 12361.
139. Yang Y, Yaccoby S, Liu W, Langford JK, Pumphrey CY, Theus A, Epstein J Sanderson RD (2002) Soluble syndecan-1 promotes growth of myeloma tumors in vivo. Blood 100, 610 617.
140. Kato M, Wang H, Kainulainen V, Fitzgerald ML, Ledbetter S, Ornitz DM Bernfield M (1998) Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2. Nat Med 4, 691 697.
141. Marshall LJ, Ramdin LS, Brooks T, DPhil PC Shute JK (2003) Plasminogen activator inhibitor-1 supports IL-8-mediated neutrophil transendothelialmigration by inhibition of the constitutive shedding of endothelial IL-8/heparan sulfate/syndecan-1 complexes. J Immunol 171, 2057 2065.
142. Munesue S, Kusano Y, Oguri K, Itano N, Yoshitomi Y, Nakanishi H, Yamashina I Okayama M (2002) The role of syndecan-2 in regulation of actin-cytoskeletal organization of Lewis lung carcinoma-derived metastatic clones. Biochem J 363, 201 209.
143. Fears CY, Gladson CL Woods A (2006) Syndecan-2 is expressed in the microvasculature of mouse gliomas and regulates angiogenesis in microvascular endothelial cells. J Biol Chem 281, 14533 14536.
144. Park H, Kim Y, Lim Y, Han I Oh ES (2002) Syndecan-2 mediates adhesion and proliferation of colon carcinoma cells. J Biol Chem 277, 29730 29736.
145. Kousidou OCh, Berdiaki A, Kletsas D, Zafiropoulos A, Theocharis AD, Tzanakakis GN Karamanos NK (2008) Estradiol-estrogen receptor: a key interplay of the expression of syndecan-2 and metalloproteinase-9 in breast cancer cells. Mol Oncol 2, 223 232.
146. Klass CM, Couchman Jr. Woods A (2000) Control of extracellular matrix assembly by syndecan-2 proteoglycan. J Cell Sci 113, 493 506.
147. Mundhenke C, Meyer K, Drew S Friedl A (2002) Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 receptor binding in breast carcinomas. Am J Pathol 160, 185 194.
148. Woods A, Longley RL, Tumova S Couchman Jr. (2000) Syndecan-4 binding to the high affinity heparin-binding domain of fibronectin drives focal adhesion formation in fibroblasts. Arch Biochem Biophys 374, 66 72.
149. Chalkiadaki G, Nikitovic D, Berdiaki A, Sifaki M, Krasagakis K, Katonis P, Karamanos NK Tzanakakis GN (2009) Fibroblast growth factor-2 modulates melanoma adhesion and migration through a syndecan-4-dependent mechanism. Int J Biochem Cell Biol 41, 1323 1331.
150. Longley RL, Woods A, Fleetwood A, Cowling GJ, Gallagher JT Couchman Jr. (1999) Control of morphology, cytoskeleton and migration by syndecan 4. J Cell Sci 112, 3421 3431.
151. Midwood KS, Mao Y, Hsia HC, Valenick LV Schwarzbauer JE (2006) Modulation of cell-fibronectin matrix interactions during tissue repair. J Investig Dermatol Symp Proc 11, 73 78.
152. Ikeda H, Hideshima T, Fulciniti M, Lutz RJ, Yasui H, Okawa Y, Kiziltepe T, Vallet S, Pozzi S, Santo L et al. (2009) The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res 15, 4028 4037.
153. Barash U, Cohen-Kapaln V, Dowek I, Sanderson RD, Ilan N Vlodavsky I (2010) Proteoglycans in health and disease: new concpts for heparanase function in tumor progression and metastasis. FEBS J 277, 3890 3903.
154. Fux L, Ilan N, Sanderson RD Vlodavsky I (2009) Heparanase: busy at the cell surface. Trends Biochem Sci 34, 511 519.
155. Kolset SO Tveit H (2008) Serglycin - structure and biology. Cell Mol Life Sci 65, 1073 1085.
156. Niemann CU, Kjeldsen L, Ralfkiaer E, Jensen MK Borregaard N (2007) Serglycin proteoglycan in hematologic malignancies: a marker of acute myeloid leukemia. Leukemia 21, 2406 2410.
157. Theocharis AD, Seidel C, Borset M, Dobra K, Baykov V, Labropoulou V, Kanakis I, Dalas E, Karamanos NK, Sundan A et al. (2006) Serglycin constitutively secreted by myeloma plasma cells is a potent inhibitor of bone mineralization in vitro. J Biol Chem 281, 35116 35128.