Skip to main content
SpringerLink
Log in

Involvement of Syndecan-1 and Heparanase in Cancer and Inflammation

  • Chapter
  • First Online:
Heparanase

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1221))

Abstract

The cell surface heparan sulfate proteoglycan Syndecan-1 acts as an important co-receptor for receptor tyrosine kinases and chemokine receptors, and as an adhesion receptor for structural glycoproteins of the extracellular matrix. It serves as a substrate for heparanase, an endo-β-glucuronidase that degrades specific domains of heparan sulfate carbohydrate chains and thereby alters the functional status of the proteoglycan and of Syndecan-1-bound ligands. Syndecan-1 and heparanase show multiple levels of functional interactions, resulting in mutual regulation of their expression, processing, and activity. These interactions are of particular relevance in the context of inflammation and malignant disease. Studies in animal models have revealed a mechanistic role of Syndecan-1 and heparanase in the regulation of contact allergies, kidney inflammation, multiple sclerosis, inflammatory bowel disease, and inflammation-associated tumorigenesis. Moreover, functional interactions between Syndecan-1 and heparanase modulate virtually all steps of tumor progression as defined in the Hallmarks of Cancer. Due to their prognostic value in cancer, and their mechanistic involvement in tumor progression, Syndecan-1 and heparanase have emerged as important drug targets. Data in preclinical models and preclinical phase I/II studies have already yielded promising results that provide a translational perspective.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Prydz, K., & Dalen, K. T. (2000). Synthesis and sorting of proteoglycans. Journal of Cell Science, 113, 193–205.

    CAS  PubMed  Google Scholar 

  2. Lamanna, W. C., et al. (2007). The heparanome—The enigma of encoding and decoding heparan sulfate sulfation. Journal of Biotechnology, 129, 290–307.

    Article  CAS  PubMed  Google Scholar 

  3. Dreyfuss, J. L., et al. (2009). Heparan sulfate proteoglycans: Structure, protein interactions and cell signaling. Anais da Academia Brasileira de Ciências, 81, 409–429.

    Article  CAS  PubMed  Google Scholar 

  4. Turnbull, J. E. (2001). Analytical and preparative strong anion-exchange HPLC of heparan sulfate and heparin saccharides. Methods Mol Biol Clifton NJ, 171, 141–147.

    CAS  Google Scholar 

  5. Nagarajan, A., Malvi, P., & Wajapeyee, N. (2018). Heparan Sulfate and Heparan Sulfate proteoglycans in Cancer initiation and progression. Frontiers in Endocrinology, 9.

    Google Scholar 

  6. Brockstedt, U., Dobra, K., Nurminen, M., & Hjerpe, A. (2002). Immunoreactivity to cell surface Syndecans in cytoplasm and nucleus: Tubulin-dependent rearrangements. Experimental Cell Research, 274, 235–245.

    Article  CAS  PubMed  Google Scholar 

  7. Piperigkou, Z., Mohr, B., Karamanos, N., & Götte, M. (2016). Shed proteoglycans in tumor stroma. Cell and Tissue Research, 365, 643–655.

    Article  CAS  PubMed  Google Scholar 

  8. Kim, C. W., Goldberger, O. A., Gallo, R. L., & Bernfield, M. (1994). Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns. Molecular Biology of the Cell, 5, 797–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sarrazin, S., Lamanna, W. C., & Esko, J. D. (2011). Heparan sulfate proteoglycans. Cold Spring Harbor Perspectives in Biology, 3.

    Google Scholar 

  10. Stepp, M. A., Pal-Ghosh, S., Tadvalkar, G., & Pajoohesh-Ganji, A. (2015). Syndecan-1 and its expanding list of contacts. Advances in Wound Care, 4, 235–249.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Afratis, N. A., et al. (2017). Syndecans - key regulators of cell signaling and biological functions. The FEBS Journal, 284, 27–41.

    Article  CAS  PubMed  Google Scholar 

  12. Altemeier, W. A., et al. (2012). Transmembrane and extracellular domains of Syndecan-1 have distinct functions in regulating lung epithelial migration and adhesion. The Journal of Biological Chemistry, 287, 34927–34935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bishop, J. R., Schuksz, M., & Esko, J. D. (2007). Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature, 446, 1030–1037.

    Article  CAS  PubMed  Google Scholar 

  14. Chakravarti, R., Sapountzi, V., & Adams, J. C. (2005). Functional role of Syndecan-1 cytoplasmic V region in Lamellipodial spreading, actin bundling, and cell migration. Molecular Biology of the Cell, 16, 3678–3691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dews, I. C., & MacKenzie, K. R. (2007). Transmembrane domains of the syndecan family of growth factor coreceptors display a hierarchy of homotypic and heterotypic interactions. Proceedings of the National Academy of Sciences, 104, 20782–20787.

    Article  CAS  Google Scholar 

  16. Langford, J. K., Stanley, M. J., Cao, D., & Sanderson, R. D. (1998). Multiple Heparan Sulfate chains are required for optimal Syndecan-1 function. The Journal of Biological Chemistry, 273, 29965–29971.

    Article  CAS  PubMed  Google Scholar 

  17. Manon-Jensen, T., Multhaupt, H. A. B., & Couchman, J. R. (2013). Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains. The FEBS Journal, 280, 2320–2331.

    Article  CAS  PubMed  Google Scholar 

  18. Teng, Y. H.-F., Aquino, R. S., & Park, P. W. (2012). Molecular functions of syndecan-1 in disease. Matrix biology : Journal of the International Society for Matrix Biology, 31, 3–16.

    Article  CAS  Google Scholar 

  19. Alexopoulou, A. N., Multhaupt, H. A. B., & Couchman, J. R. (2007). Syndecans in wound healing, inflammation and vascular biology. The International Journal of Biochemistry & Cell Biology, 39, 505–528.

    Article  CAS  Google Scholar 

  20. Haynes, A., et al. (2005). Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis. Infection and Immunity, 73, 7914–7921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mali, M., Andtfolk, H., Miettinen, H. M., & Jalkanen, M. (1994). Suppression of tumor cell growth by syndecan-1 ectodomain. The Journal of Biological Chemistry, 269, 27795–27798.

    CAS  PubMed  Google Scholar 

  22. Nikolova, V., et al. (2009). Differential roles for membrane-bound and soluble syndecan-1 (CD138) in breast cancer progression. Carcinogenesis, 30, 397–407.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang, L. (2010). Glycosaminoglycan (GAG) biosynthesis and GAG-binding proteins. Progress in Molecular Biology and Translational Science, 93, 1–17.

    Article  CAS  PubMed  Google Scholar 

  24. Fairbanks, M. B., et al. (1999). Processing of the human Heparanase precursor and evidence that the active enzyme is a heterodimer. The Journal of Biological Chemistry, 274, 29587–29590.

    Article  CAS  PubMed  Google Scholar 

  25. Abboud-Jarrous, G., et al. (2005). Site-directed mutagenesis, Proteolytic cleavage, and activation of human Proheparanase. The Journal of Biological Chemistry, 280, 13568–13575.

    Article  CAS  PubMed  Google Scholar 

  26. Levy-Adam, F., Miao, H.-Q., Heinrikson, R. L., Vlodavsky, I., & Ilan, N. (2003). Heterodimer formation is essential for heparanase enzymatic activity. Biochemical and Biophysical Research Communications, 308, 885–891.

    Article  CAS  PubMed  Google Scholar 

  27. Gingis-Velitski, S., Zetser, A., Flugelman, M. Y., Vlodavsky, I., & Ilan, N. (2004). Heparanase induces endothelial cell migration via protein kinase B/Akt activation. The Journal of Biological Chemistry, 279, 23536–23541.

    Article  CAS  PubMed  Google Scholar 

  28. Doviner, V., et al. (2006). Spatial and temporal heparanase expression in colon mucosa throughout the adenoma-carcinoma sequence. Modern Pathology, 19, 878–888.

    Article  CAS  PubMed  Google Scholar 

  29. Zetser, A., Bashenko, Y., Miao, H.-Q., Vlodavsky, I., & Ilan, N. (2003). Heparanase affects adhesive and tumorigenic potential of human Glioma cells. Cancer Research, 63, 7733–7741.

    CAS  PubMed  Google Scholar 

  30. Cohen-Kaplan, V., Doweck, I., Naroditsky, I., Vlodavsky, I., & Ilan, N. (2008). Heparanase augments epidermal growth factor receptor phosphorylation: Correlation with head and neck tumor progression. Cancer Research, 68, 10077–10085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cohen-Kaplan, V., et al. (2008). Heparanase induces VEGF C and facilitates tumor lymphangiogenesis. International Journal of Cancer, 123, 2566–2573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sanderson, R. D., Elkin, M., Rapraeger, A. C., Ilan, N., & Vlodavsky, I. (2017). Heparanase regulation of cancer, autophagy and inflammation: New mechanisms and targets for therapy. The FEBS Journal, 284, 42–55.

    Article  CAS  PubMed  Google Scholar 

  33. Jin, H., & Zhou, S. (2017). The functions of Heparanase in human diseases. Mini Reviews in Medicinal Chemistry, 17, 541–548.

    Article  CAS  PubMed  Google Scholar 

  34. Masola, V., Bellin, G., Gambaro, G., & Onisto, M. (2018). Heparanase: A multitasking protein involved in Extracellular Matrix (ECM) Remodeling and intracellular events. Cell, 7, 236.

    Article  CAS  Google Scholar 

  35. Lamorte, S., et al. (2012). Syndecan-1 promotes the angiogenic phenotype of multiple myeloma endothelial cells. Leukemia, 26, 1081–1090.

    Article  CAS  PubMed  Google Scholar 

  36. Noguer, O., Villena, J., Lorita, J., Vilaró, S., & Reina, M. (2009). Syndecan-2 downregulation impairs angiogenesis in human microvascular endothelial cells. Experimental Cell Research, 315, 795–808.

    Article  CAS  PubMed  Google Scholar 

  37. De Rossi, G., & Whiteford, J. R. (2013). A novel role for syndecan-3 in angiogenesis. F1000Research, 2, 270.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Ramani, V. C., Pruett, P. S., Thompson, C. A., DeLucas, L. D., & Sanderson, R. D. (2012). Heparan Sulfate chains of Syndecan-1 regulate Ectodomain shedding. The Journal of Biological Chemistry, 287, 9952–9961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ma, P., et al. (2006). Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin. The Journal of Cell Biology, 174, 1097–1106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Levy-Adam, F., Feld, S., Suss-Toby, E., Vlodavsky, I., & Ilan, N. (2008). Heparanase facilitates cell adhesion and spreading by clustering of cell surface Heparan Sulfate proteoglycans. PLoS One, 3, e2319.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Bernfield, M., et al. (1999). Functions of cell surface Heparan Sulfate proteoglycans. Annual Review of Biochemistry, 68, 729–777.

    Article  CAS  PubMed  Google Scholar 

  42. Elenius, V., Götte, M., Reizes, O., Elenius, K., & Bernfield, M. (2004). Inhibition by the soluble Syndecan-1 Ectodomains delays wound repair in mice overexpressing Syndecan-1. The Journal of Biological Chemistry, 279, 41928–41935.

    Article  CAS  PubMed  Google Scholar 

  43. Manon-Jensen, T., Itoh, Y., & Couchman, J. R. (2010). Proteoglycans in health and disease: The multiple roles of syndecan shedding. The FEBS Journal, 277, 3876–3889.

    Article  CAS  PubMed  Google Scholar 

  44. Nam, E. J., & Park, P. W. (2012). Shedding of cell membrane-bound Proteoglycans. In F. Rédini (Ed.), Proteoglycans: Methods and protocols (pp. 291–305). Humana Press. https://doi.org/10.1007/978-1-61779-498-8_19.

  45. Yang, Y., et al. (2007). Heparanase enhances syndecan-1 shedding: A novel mechanism for stimulation of tumor growth and metastasis. The Journal of Biological Chemistry, 282, 13326–13333.

    Article  CAS  PubMed  Google Scholar 

  46. Mahtouk, K., et al. (2007). Heparanase influences expression and shedding of syndecan-1, and its expression by the bone marrow environment is a bad prognostic factor in multiple myeloma. Blood, 109, 4914–4923.

    Article  CAS  PubMed  Google Scholar 

  47. Ramani, V. C., et al. (2013). The heparanase/syndecan-1 axis in cancer: Mechanisms and therapies. The FEBS Journal, 280, 2294–2306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pasqualon, T., et al. (2015). A cytoplasmic C-terminal fragment of syndecan-1 is generated by sequential proteolysis and antagonizes syndecan-1 dependent lung tumor cell migration. Oncotarget, 6, 31295–31312.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Jung, O., et al. (2016). Heparanase-induced shedding of syndecan-1/CD138 in myeloma and endothelial cells activates VEGFR2 and an invasive phenotype: Prevention by novel synstatins. Oncogene, 5, e202.

    Article  CAS  Google Scholar 

  50. Purushothaman, A., et al. (2010). Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis. Blood, 115, 2449–2457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ritchie, J. P., et al. (2011). SST0001, a chemically modified heparin, inhibits myeloma growth and angiogenesis via disruption of the Heparanase/Syndecan-1 Axis. Clinical Cancer Research, 17, 1382–1393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Purushothaman, A., Chen, L., Yang, Y., & Sanderson, R. D. (2008). Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma. The Journal of Biological Chemistry, 283, 32628–32636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sotnikov, I., et al. (2004). Enzymatically quiescent Heparanase augments T cell interactions with VCAM-1 and extracellular matrix components under versatile dynamic contexts. Journal of Immunology, 172, 5185–5193.

    Article  CAS  Google Scholar 

  54. Götte, M. (2003). Syndecans in inflammation. The FASEB Journal, 17, 575–591.

    Article  PubMed  Google Scholar 

  55. Götte, M., & Echtermeyer, F. (2003). Syndecan-1 as a regulator of chemokine function. The Scientific World Journal. https://doi.org/10.1100/tsw.2003.118.

  56. Stewart, M. D., Ramani, V. C., & Sanderson, R. D. (2015). Shed Syndecan-1 Translocates to the nucleus of cells delivering growth factors and inhibiting histone acetylation a novel mechanism of tumor-host cross-talk. The Journal of Biological Chemistry, 290, 941–949.

    Article  CAS  PubMed  Google Scholar 

  57. Kovalszky, I., Hjerpe, A., & Dobra, K. (2014). Nuclear translocation of heparan sulfate proteoglycans and their functional significance. Biochimica et Biophysica Acta (BBA) – General Subjects, 1840, 2491–2497.

    Article  CAS  Google Scholar 

  58. Leadbeater, W. E., et al. (2006). Intracellular trafficking in neurones and glia of fibroblast growth factor-2, fibroblast growth factor receptor 1 and heparan sulphate proteoglycans in the injured adult rat cerebral cortex. Journal of Neurochemistry, 96, 1189–1200.

    Article  CAS  PubMed  Google Scholar 

  59. Schrage, Y. M., et al. (2009). Aberrant Heparan Sulfate proteoglycan localization, despite Normal Exostosin, in central Chondrosarcoma. The American Journal of Pathology, 174, 979–988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Schubert, S. Y., et al. (2004). Human heparanase nuclear localization and enzymatic activity. Laboratory Investigation, 84, 535–544.

    Article  CAS  PubMed  Google Scholar 

  61. Zong, F., et al. (2009). Syndecan-1 and FGF-2, but not FGF Receptor-1, share a common transport route and co-localize with Heparanase in the nuclei of Mesenchymal tumor cells. PLoS One, 4, e7346.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Richardson, T. P., Trinkaus-Randall, V., & Nugent, M. A. (2001). Regulation of heparan sulfate proteoglycan nuclear localization by fibronectin. Journal of Cell Science, 114, 1613–1623.

    CAS  PubMed  Google Scholar 

  63. Hsia, E., Richardson, T. P., & Nugent, M. A. (2003). Nuclear localization of basic fibroblast growth factor is mediated by heparan sulfate proteoglycans through protein kinase C signaling. Journal of Cellular Biochemistry, 88, 1214–1225.

    Article  CAS  PubMed  Google Scholar 

  64. Fedarko, N. S., Ishihara, M., & Conrad, H. E. (1989). Control of cell division in hepatoma cells by exogenous heparan sulfate proteoglycan. Journal of Cellular Physiology, 139, 287–294.

    Article  CAS  PubMed  Google Scholar 

  65. Baldin, V., Roman, A. M., Bosc-Bierne, I., Amalric, F., & Bouche, G. (1990). Translocation of bFGF to the nucleus is G1 phase cell cycle specific in bovine aortic endothelial cells. The EMBO Journal, 9, 1511–1517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Roghani, M., & Moscatelli, D. (1992). Basic fibroblast growth factor is internalized through both receptor-mediated and heparan sulfate-mediated mechanisms. The Journal of Biological Chemistry, 267, 22156–22162.

    CAS  PubMed  Google Scholar 

  67. Zong, F., et al. (2011). Specific Syndecan-1 domains regulate Mesenchymal tumor cell adhesion, motility and migration. PLoS One, 6, e14816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kovalszky, I., et al. (1998). Inhibition of DNA topoisomerase I activity by heparan sulfate and modulation by basic fibroblast growth factor. Molecular and Cellular Biochemistry, 183, 11–23.

    Article  CAS  PubMed  Google Scholar 

  69. Chen, L., & Sanderson, R. D. (2009). Heparanase regulates levels of Syndecan-1 in the nucleus. PLoS One, 4, e4947.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Purushothaman, A., et al. (2011). Heparanase-mediated loss of nuclear Syndecan-1 enhances histone Acetyltransferase (HAT) activity to promote expression of genes that drive an aggressive tumor phenotype. The Journal of Biological Chemistry, 286, 30377–30383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhang, L., Sullivan, P., Suyama, J., & Marchetti, D. (2010). Epidermal growth factor-induced heparanase nucleolar localization augments DNA topoisomerase I activity in brain metastatic breast cancer. Molecular Cancer Research, 8, 278–290.

    Article  CAS  PubMed  Google Scholar 

  72. Gould, G. W., & Lippincott-Schwartz, J. (2009). New roles for endosomes: From vesicular carriers to multi-purpose platforms. Nature Reviews. Molecular Cell Biology, 10, 287–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Klumperman, J., & Raposo, G. (2014). The complex ultrastructure of the Endolysosomal system. Cold Spring Harbor Perspectives in Biology, 6, a016857.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Henne, W. M., Buchkovich, N. J., & Emr, S. D. (2011). The ESCRT pathway. Developmental Cell, 21, 77–91.

    Article  CAS  PubMed  Google Scholar 

  75. Hanson, P. I., & Cashikar, A. (2012). Multivesicular body morphogenesis. Annual Review of Cell and Developmental Biology, 28, 337–362.

    Article  CAS  PubMed  Google Scholar 

  76. Baietti, M. F., et al. (2012). Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nature Cell Biology, 14, 677–685.

    Article  CAS  PubMed  Google Scholar 

  77. Peinado, H., Lavotshkin, S., & Lyden, D. (2011). The secreted factors responsible for pre-metastatic niche formation: Old sayings and new thoughts. Seminars in Cancer Biology, 21, 139–146.

    Article  CAS  PubMed  Google Scholar 

  78. Ostrowski, M., et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nature Cell Biology, 12, 19–30.

    Article  CAS  PubMed  Google Scholar 

  79. Grootjans, J. J., Reekmans, G., Ceulemans, H., & David, G. (2000). Syntenin-Syndecan binding requires Syndecan-Synteny and the co-operation of both PDZ domains of Syntenin. The Journal of Biological Chemistry, 275, 19933–19941.

    Article  CAS  PubMed  Google Scholar 

  80. Zimmermann, P., et al. (2001). Characterization of Syntenin, a Syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments. Molecular Biology of the Cell, 12, 339–350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Thompson, C. A., Purushothaman, A., Ramani, V. C., Vlodavsky, I., & Sanderson, R. D. (2013). Heparanase regulates secretion, composition, and function of tumor cell-derived Exosomes. The Journal of Biological Chemistry, 288, 10093–10099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Roucourt, B., Meeussen, S., Bao, J., Zimmermann, P., & David, G. (2015). Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell Research, 25, 412–428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. David, G., & Zimmermann, P. (2016). Heparanase tailors syndecan for exosome production. Molecular & Cellular Oncology, 3, e1047556.

    Article  CAS  Google Scholar 

  84. Friand, V., David, G., & Zimmermann, P. (2015). Syntenin and syndecan in the biogenesis of exosomes. Biology of the Cell, 107, 331–341.

    Article  CAS  PubMed  Google Scholar 

  85. Keller, S., et al. (2009). Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Letters, 278, 73–81.

    Article  CAS  PubMed  Google Scholar 

  86. Beauvais, D. M., Ell, B. J., McWhorter, A. R., & Rapraeger, A. C. (2009). Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. The Journal of Experimental Medicine, 206, 691–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Beauvais, D. M., & Rapraeger, A. C. (2010). Syndecan-1 couples the insulin-like growth factor-1 receptor to inside-out integrin activation. Journal of Cell Science, 123, 3796–3807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Beauvais, D. M., Jung, O., Yang, Y., Sanderson, R. D., & Rapraeger, A. C. (2016). Syndecan-1 (CD138) suppresses apoptosis in multiple myeloma by activating IGF1 receptor: Prevention by SynstatinIGF1R inhibits tumor growth. Cancer Research, 76, 4981–4993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Rapraeger, A. C. (2013). Synstatin: A selective inhibitor of the syndecan-1-coupled IGF1R–αvβ3 integrin complex in tumorigenesis and angiogenesis. The FEBS Journal, 280, 2207–2215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang, H., Jin, H., & Rapraeger, A. C. (2015). Syndecan-1 and Syndecan-4 Capture epidermal growth factor receptor family members and the α3β1 integrin via binding sites in their Ectodomains novel synstatins prevent kinase capture and inhibit α6β4-integrin-dependent epithelial cell motility. The Journal of Biological Chemistry, 290, 26103–26113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Belting, M. (2003). Heparan sulfate proteoglycan as a plasma membrane carrier. Trends in Biochemical Sciences, 28, 145–151.

    Article  CAS  PubMed  Google Scholar 

  92. Olsnes, S., Klingenberg, O., & Wiedłocha, A. (2003). Transport of Exogenous Growth Factors and Cytokines to the Cytosol and to the Nucleus. Physiological Reviews, 83, 163–182.

    Article  CAS  PubMed  Google Scholar 

  93. Keresztes, M., & Boonstra, J. (1999). Import(ance) of growth factors in(to) the nucleus. The Journal of Cell Biology, 145, 421–424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Belting, M., Sandgren, S., & Wittrup, A. (2005). Nuclear delivery of macromolecules: Barriers and carriers. Advanced Drug Delivery Reviews, 57, 505–527.

    Article  CAS  PubMed  Google Scholar 

  95. Chen, K., & Williams, K. J. (2013). Molecular mediators for raft-dependent endocytosis of Syndecan-1, a highly conserved, multifunctional receptor. Journal of Biological Chemistry, 288, 13988–13999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ramani, V. C., Yang, Y., Ren, Y., Nan, L., & Sanderson, R. D. (2011). Heparanase plays a dual role in driving Hepatocyte Growth Factor (HGF) signaling by enhancing HGF expression and activity. The Journal of Biological Chemistry, 286, 6490–6499.

    Article  CAS  PubMed  Google Scholar 

  97. Derksen, P. W. B., et al. (2002). Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes met signaling in multiple myeloma. Blood, 99, 1405–1410.

    Article  CAS  PubMed  Google Scholar 

  98. Deakin, J. A., & Lyon, M. (1999). Differential regulation of hepatocyte growth factor/scatter factor by cell surface proteoglycans and free glycosaminoglycan chains. Journal of Cell Science, 112, 1999–2009.

    CAS  PubMed  Google Scholar 

  99. Seidel, C., et al. (2000). High levels of soluble syndecan-1 in myeloma-derived bone marrow: Modulation of hepatocyte growth factor activity. Blood, 96, 3139–3146.

    Article  CAS  PubMed  Google Scholar 

  100. Brooks, P. C., Clark, R. A., & Cheresh, D. A. (1994). Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science, 264, 569–571.

    Article  CAS  PubMed  Google Scholar 

  101. Mahabeleshwar, G. H., Feng, W., Reddy, K., Plow, E. F., & Byzova, T. V. (2007). Mechanisms of integrin–vascular endothelial growth factor receptor cross-activation in angiogenesis. Circulation Research, 101, 570–580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Reiland, J., Kempf, D., Roy, M., Denkins, Y., & Marchetti, D. (2006). FGF2 binding, Signaling, and angiogenesis are modulated by Heparanase in metastatic melanoma cells. Neoplasia N. Y. N, 8, 596–606.

    Article  CAS  Google Scholar 

  103. Kato, M., et al. (1998). Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2. Nature Medicine, 4, 691–697.

    Article  CAS  PubMed  Google Scholar 

  104. Liu, D., Shriver, Z., Venkataraman, G., Shabrawi, Y. E., & Sasisekharan, R. (2002). Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis. Proceedings of the National Academy of Sciences, 99, 568–573.

    Article  CAS  Google Scholar 

  105. Masola, V., et al. (2012). Heparanase and Syndecan-1 interplay orchestrates fibroblast growth Factor-2-induced epithelial-Mesenchymal transition in renal tubular cells. The Journal of Biological Chemistry, 287, 1478–1488.

    Article  CAS  PubMed  Google Scholar 

  106. Margraf, A., Ley, K., & Zarbock, A. (2019 July). Neutrophil recruitment: From model systems to tissue-specific patterns. Trends in Immunology, 40(7), 613–634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Borsig, L. (2018, September 1). Selectins in cancer immunity. Glycobiology, 28(9), 648–655.

    Article  CAS  PubMed  Google Scholar 

  108. Kumar, A. V., Katakam, S. K., Urbanowitz, A. K., & Gotte, M. (2015). Heparan sulphate as a regulator of leukocyte recruitment in inflammation. Current Protein & Peptide Science, 16(1), 77–86.

    Article  CAS  Google Scholar 

  109. Schlessinger, J., Plotnikov, A. N., Ibrahimi, O. A., Eliseenkova, A. V., Yeh, B. K., Yayon, A., Linhardt, R. J., & Mohammadi, M. (2000). Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Molecular Cell, 6, 743–750.

    Article  CAS  PubMed  Google Scholar 

  110. Lortat-Jacob, H. (2009). The molecular basis and functional implications of chemokine interactions with heparan sulfate. Current Opinion in Structural Biology, 19, 543–548.

    Article  CAS  PubMed  Google Scholar 

  111. Hayashida, K., Parks, W. C., & Park, P. W. (2009). Syndecan-1 shedding facilitates the resolution of neutrophilic inflammation by removing sequestered CXC chemokines. Blood, 114, 3033–3043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hoogewerf, A. J., Kuschert, G. S., Proudfoot, A. E., Borlat, F., Clark-Lewis, I., Power, C. A., & Wells, T. N. (1997). Glycosaminoglycans mediate cell surface oligomerization of chemokines. Biochemistry, 36, 13570–13578.

    Article  CAS  PubMed  Google Scholar 

  113. Stoler-Barak, L., Moussion, C., Shezen, E., Hatzav, M., Sixt, M., & Alon, R. (2014, January 22). Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects. PLoS One, 9(1), e85699.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Wang, L., Fuster, M., Sriramarao, P., & Esko, J. D. (2005). Endothelial heparan sulfate deficiency impairs L-selectin- and chemokinemediated neutrophil trafficking during inflammatory responses. Nature Immunology, 6, 902–910.

    Article  CAS  PubMed  Google Scholar 

  115. Massena, S., Christoffersson, G., Hjertstrom, E., Zcharia, E., Vlodavsky, I., Ausmees, N., Rolny, C., Li, J. P., & Phillipson, M. (2010). A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood, 116, 1924–1931.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Götte, M., Joussen, A. M., Klein, C., Andre, P., Wagner, D. D., Hinkes, M. T., Kirchhof, B., Adamis, A. P., & Bernfield, M. (2002, April). Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature. Investigative Ophthalmology & Visual Science, 43(4), 1135–1141.

    Google Scholar 

  117. Götte, M., Bernfield, M., & Joussen, A. M. (2005, June). Increased leukocyte-endothelial interactions in syndecan-1-deficient mice involve heparan sulfate-dependent and -independent steps. Current Eye Research, 30(6), 417–422.

    Article  PubMed  CAS  Google Scholar 

  118. Floer, M., Götte, M., Wild, M. K., Heidemann, J., Gassar, E. S., Domschke, W., Kiesel, L., Luegering, A., & Kucharzik, T. (2010, January). Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice. The American Journal of Pathology, 176(1), 146–157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Kharabi Masouleh, B., Ten Dam, G. B., Wild, M. K., Seelige, R., van der Vlag, J., Rops, A. L., Echtermeyer, F. G., Vestweber, D., van Kuppevelt, T. H., Kiesel, L., & Götte, M. (2009, April 15). Role of the heparan sulfate proteoglycan syndecan-1 (CD138) in delayed-type hypersensitivity. Journal of Immunology, 182(8), 4985–4993.

    Article  CAS  Google Scholar 

  120. Lever, R., Rose, M. J., McKenzie, E. A., & Page, C. P. (2014, June 15). Heparanase induces inflammatory cell recruitment in vivo by promoting adhesion to vascular endothelium. American Journal of Physiology. Cell Physiology, 306(12), C1184–C1190.

    Article  CAS  PubMed  Google Scholar 

  121. Stoler-Barak, L., Petrovich, E., Aychek, T., Gurevich, I., Tal, O., Hatzav, M., Ilan, N., Feigelson, S. W., Shakhar, G., Vlodavsky, I., & Alon, R. (2015). Heparanase of murine effector lymphocytes and neutrophils is not required for their diapedesis into sites of inflammation. FASEB Journal, 29, 2010–2021.

    Article  CAS  PubMed  Google Scholar 

  122. Schmidt, E. P., Yang, Y., Janssen, W. J., Gandjeva, A., Perez, M. J., Barthel, L., Zemans, R. L., Bowman, J. C., Koyanagi, D. E., Yunt, Z. X., Smith, L. P., Cheng, S. S., Overdier, K. H., Thompson, K. R., Geraci, M. W., Douglas, I. S., Pearse, D. B., & Tuder, R. M. (2012). The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nature Medicine, 18, 1217–1223.

    Article  CAS  PubMed  Google Scholar 

  123. Chen, X., Jiang, W., Yue, C., Zhang, W., Tong, C., Dai, D., Cheng, B., Huang, C., & Lu, L. (2017, September 16). Heparanase contributes to trans-endothelial migration of hepatocellular carcinoma cells. Journal of Cancer, 8(16), 3309–3317.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Grabbe, S., & Schwarz, T. (1998). Immunoregulatory mechanisms involved in elicitation of allergic contact hypersensitivity. Immunology Today, 19, 37–44.

    Article  CAS  PubMed  Google Scholar 

  125. Seidler, D. G., Mohamed, N. A., Bocian, C., Stadtmann, A., Hermann, S., Schäfers, K., Schäfers, M., Iozzo, R. V., Zarbock, A., & Götte, M. (2011, December 1). The role for decorin in delayed-type hypersensitivity. Journal of Immunology, 187(11), 6108–6119.

    Article  CAS  Google Scholar 

  126. Averbeck, M., Kuhn, S., Bühligen, J., Götte, M., Simon, J. C., & Polte, T. (2017, November). Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens. Experimental Dermatology, 26(11), 1060–1067.

    Article  CAS  PubMed  Google Scholar 

  127. Edovitsky, E., Lerner, I., Zcharia, E., Peretz, T., Vlodavsky, I., & Elkin, M. (2006, May 1). Role of endothelial heparanase in delayed-type hypersensitivity. Blood, 107(9), 3609–3616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Reynolds, J. (2011, June). Strain differences and the genetic basis of experimental autoimmune anti-glomerular basement membrane glomerulonephritis. International Journal of Experimental Pathology, 92(3), 211–217.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Rops, A. L., Götte, M., Baselmans, M. H., van den Hoven, M. J., Steenbergen, E. J., Lensen, J. F., Wijnhoven, T. J., Cevikbas, F., van den Heuvel, L. P., van Kuppevelt, T. H., Berden, J. H., & van der Vlag, J. (2007, November). Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis. Kidney International, 72(10), 1204–1215.

    Article  CAS  PubMed  Google Scholar 

  130. Garsen, M., Benner, M., Dijkman, H. B., van Kuppevelt, T. H., Li, J. P., Rabelink, T. J., Vlodavsky, I., Berden, J. H., Rops, A. L., Elkin, M., & van der Vlag, J. (2016, April). Heparanase is essential for the development of acute experimental glomerulonephritis. The American Journal of Pathology, 186(4), 805–815.

    Article  CAS  PubMed  Google Scholar 

  131. Begolka, W. S., Vanderlugt, C. L., Rahbe, S. M., & Miller, S. D. (1998). Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis. Journal of Immunology, 161, 4437–4446.

    CAS  Google Scholar 

  132. Hemmer, B., Archelos, J. J., & Hartung, H. P. (2002). New concepts in the immunopathogenesis of multiple sclerosis. Nature Reviews. Neuroscience, 3, 291–301.

    Article  CAS  PubMed  Google Scholar 

  133. Zhang, X., Wu, C., Song, J., Götte, M., & Sorokin, L. (2013, November 1). Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis. Journal of Immunology, 191(9), 4551–4561.

    Article  CAS  Google Scholar 

  134. Bitan, M., Weiss, L., Reibstein, I., Zeira, M., Fellig, Y., Slavin, S., Zcharia, E., Nagler, A., & Vlodavsky, I. (2010, June). Heparanase upregulates Th2 cytokines, ameliorating experimental autoimmune encephalitis. Molecular Immunology, 47(10), 1890–1898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Blander, J. M. (2016, July). Death in the intestinal epithelium-basic biology and implications for inflammatory bowel disease. The FEBS Journal, 283(14), 2720–2730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Eichele, D. D., & Kharbanda, K. K. (2017, September 7). Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World Journal of Gastroenterology, 23(33), 6016–6029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Day, R., Ilyas, M., Daszak, P., Talbot, I., & Forbes, A. (1999, December). Expression of syndecan-1 in inflammatory bowel disease and a possible mechanism of heparin therapy. Digestive Diseases and Sciences, 44(12), 2508–2515.

    Article  CAS  PubMed  Google Scholar 

  138. Lopez, A., Pouillon, L., Beaugerie, L., Danese, S., & Peyrin-Biroulet, L. (2018 February – April). Colorectal cancer prevention in patients with ulcerative colitis. Best Practice & Research Clinical Gastroenterology, 32–33, 103–109.

    Article  Google Scholar 

  139. Pap, Z., Pávai, Z., Dénes, L., Kovalszky, I., & Jung, J. (2009, December). An immunohistochemical study of colon adenomas and carcinomas: E-cadherin, Syndecan-1, Ets-1. Pathology Oncology Research, 15(4), 579–587.

    Article  CAS  PubMed  Google Scholar 

  140. Peretti, T., Waisberg, J., Mader, A. M., de Matos, L. L., da Costa, R. B., Conceição, G. M., Lopes, A. C., Nader, H. B., & Pinhal, M. A. (2008, August). Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma. European Journal of Gastroenterology & Hepatology, 20(8), 756–765.

    Article  CAS  Google Scholar 

  141. Snider, A. J., Bialkowska, A. B., Ghaleb, A. M., Yang, V. W., Obeid, L. M., & Hannun, Y. A. (2016). Murine model for colitis-associated Cancer of the Colon. Methods in Molecular Biology, 1438, 245–254.

    Article  CAS  PubMed  Google Scholar 

  142. Binder Gallimidi, A., Nussbaum, G., Hermano, E., Weizman, B., Meirovitz, A., Vlodavsky, I., Götte, M., Elkin, M. (2017, March 28). Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma. PLoS One; 12(3):e0174343. https://doi.org/10.1371/journal.pone.0174343. eCollection 2017.

  143. Waterman, M., Ben-Izhak, O., Eliakim, R., Groisman, G., Vlodavsky, I., & Ilan, N. (2007, January). Heparanase upregulation by colonic epithelium in inflammatory bowel disease. Modern Pathology, 20(1), 8–14.

    Article  CAS  PubMed  Google Scholar 

  144. Friedmann, Y., Vlodavsky, I., Aingorn, H., Aviv, A., Peretz, T., Pecker, I., & Pappo, O. (2000, October). Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. The American Journal of Pathology, 157(4), 1167–1175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Lerner, I., Hermano, E., Zcharia, E., Rodkin, D., Bulvik, R., Doviner, V., Rubinstein, A. M., Ishai-Michaeli, R., Atzmon, R., Sherman, Y., Meirovitz, A., Peretz, T., Vlodavsky, I., & Elkin, M. (2011, May). Heparanase powers a chronic inflammatory circuit that promotes colitis-associated tumorigenesis in mice. The Journal of Clinical Investigation, 121(5), 1709–1721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Hanahan, D., & Weinberg, R. A. (2000, January 7). The hallmarks of cancer. Cell, 100(1), 57–70.

    Article  CAS  PubMed  Google Scholar 

  147. Hanahan, D., & Weinberg, R. A. (2011, March 4). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674.

    Article  CAS  PubMed  Google Scholar 

  148. Espinoza-Sánchez, N. A., & Götte, M. (2019, July 20) Role of cell surface proteoglycans in cancer immunotherapy. Seminars in Cancer Biology. pii: S1044-579X(19)30041–0. https://doi.org/10.1016/j.semcancer.2019.07.012. [Epub ahead of print] Review.PMID:31336150.

  149. Ibrahim, S. A., Hassan, H., & Götte, M. (2014, November). MicroRNA regulation of proteoglycan function in cancer. The FEBS Journal, 281(22), 5009–5022.

    Article  CAS  PubMed  Google Scholar 

  150. Kato, M., Wang, H., Kainulainen, V., Fitzgerald, M. L., Ledbetter, S., Ornitz, D. M., & Bernfield, M. (1998, June). Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2. Nature Medicine, 4(6), 691–697.

    Article  CAS  PubMed  Google Scholar 

  151. Vlodavsky, I., Gross-Cohen, M., Weissmann, M., Ilan, N., & Sanderson, R. D. (2018, January). Opposing functions of Heparanase-1 and Heparanase-2 in Cancer progression. Trends in Biochemical Sciences, 43(1), 18–31.

    Article  CAS  PubMed  Google Scholar 

  152. Regős, E., Abdelfattah, H. H., Reszegi, A., Szilák, L., Werling, K., Szabó, G., Kiss, A., Schaff, Z., Kovalszky, I., & Baghy, K. (2018, August). Syndecan-1 inhibits early stages of liver fibrogenesis by interfering with TGFβ1 action and upregulating MMP14. Matrix Biology, 68–69, 474–489.

    Article  PubMed  CAS  Google Scholar 

  153. Zeng, Y., Yao, X., Chen, L., Yan, Z., Liu, J., Zhang, Y., Feng, T., Wu, J., & Liu, X. (2016, September 27). Sphingosine-1-phosphate induced epithelial-mesenchymal transition of hepatocellular carcinoma via an MMP-7/ syndecan-1/TGF-β autocrine loop. Oncotarget, 7(39), 63324–63337.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Vitale, D., Kumar Katakam, S., Greve, B., Jang, B., Oh, E. S., Alaniz, L., & Götte, M. (2019, August). Proteoglycans and glycosaminoglycans as regulators of cancer stem cell function and therapeutic resistance. The FEBS Journal, 286(15), 2870–2882.

    Article  CAS  PubMed  Google Scholar 

  155. McDermott, S. P., Ranheim, E. A., Leatherberry, V. S., Khwaja, S. S., Klos, K. S., & Alexander, C. M. (2007, March 1). Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor development. Oncogene, 26(10), 1407–1416.

    Article  CAS  PubMed  Google Scholar 

  156. Liu, B. Y., McDermott, S. P., Khwaja, S. S., & Alexander, C. M. (2004, March 23). The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proceedings of the National Academy of Sciences of the United States of America, 101(12), 4158–4163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Ibrahim, S. A., Hassan, H., Vilardo, L., Kumar, S. K., Kumar, A. V., Kelsch, R., Schneider, C., Kiesel, L., Eich, H. T., Zucchi, I., Reinbold, R., Greve, B., & Götte, M. (2013, December 31). Syndecan-1 (CD138) modulates triple-negative breast cancer stem cell properties via regulation of LRP-6 and IL-6-mediated STAT3 signaling. PLoS One, 8(12), e85737.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Ibrahim, S. A., Gadalla, R., El-Ghonaimy, E. A., Samir, O., Mohamed, H. T., Hassan, H., Greve, B., El-Shinawi, M., Mohamed, M. M., & Götte, M. (2017, March 7). Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, notch and EGFR signaling pathways. Molecular Cancer, 16(1), 57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Ibrahim, S. A., Yip, G. W., Stock, C., Pan, J. W., Neubauer, C., Poeter, M., Pupjalis, D., Koo, C. Y., Kelsch, R., Schüle, R., Rescher, U., Kiesel, L., & Götte, M. (2012, September 15). Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a rho-GTPase- and E-cadherin-dependent mechanism. International Journal of Cancer, 131(6), E884–E896.

    Article  CAS  PubMed  Google Scholar 

  160. Nobuhisa, T., Naomoto, Y., Takaoka, M., Tabuchi, Y., Ookawa, K., Kitamoto, D., Gunduz, E., Gunduz, M., Nagatsuka, H., Haisa, M., Matsuoka, J., Nakajima, M., & Tanaka, N. (2005, May 27). Emergence of nuclear heparanase induces differentiation of human mammary cancer cells. Biochemical and Biophysical Research Communications, 331(1), 175–180.

    Article  CAS  PubMed  Google Scholar 

  161. Spiegel, A., Zcharia, E., Vagima, Y., Itkin, T., Kalinkovich, A., Dar, A., Kollet, O., Netzer, N., Golan, K., Shafat, I., Ilan, N., Nagler, A., Vlodavsky, I., & Lapidot, T. (2008, May 15). Heparanase regulates retention and proliferation of primitive Sca-1+/c-kit+/Lin- cells via modulation of the bone marrow microenvironment. Blood, 111(10):4934–4943. https://doi.org/10.1182/blood-2007-10-116145. Epub 2008 Mar 11.

  162. Cheng, C. C., Lee, Y. H., Lin, S. P., Huangfu, W. C., & Liu, I. H. (2014, March 13). Cell-autonomous heparanase modulates self-renewal and migration in bone marrow-derived mesenchymal stem cells. Journal of Biomedical Science, 21, 21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Ruan, J., Trotter, T. N., Nan, L., Luo, R., Javed, A., Sanderson, R. D., Suva, L. J., & Yang, Y. (2013, November). Heparanase inhibits osteoblastogenesis and shifts bone marrow progenitor cell fate in myeloma bone disease. Bone, 57(1):10–17. https://doi.org/10.1016/j.bone.2013.07.024. Epub 2013 Jul 27.

  164. Xiong, A., Kundu, S., Forsberg, M., Xiong, Y., Bergström, T., Paavilainen, T., Kjellén, L., Li, J. P., & Forsberg-Nilsson, K. (2017, October). Heparanase confers a growth advantage to differentiating murine embryonic stem cells, and enhances oligodendrocyte formation. Matrix Biology, 62, 92–104.

    Article  CAS  PubMed  Google Scholar 

  165. Choi, D. S., Kim, J. H., Ryu, H. S., Kim, H. C., Han, J. H., Lee, J. S., & Min, C. K. (2007, August 15). Syndecan-1, a key regulator of cell viability in endometrial cancer. International Journal of Cancer, 121(4), 741–750.

    Article  CAS  PubMed  Google Scholar 

  166. Sun, H., Hu, Y., Gu, Z., Owens, R. T., Chen, Y. Q., & Edwards, I. J. (2011, October). Omega-3 fatty acids induce apoptosis in human breast cancer cells and mouse mammary tissue through syndecan-1 inhibition of the MEK-Erk pathway. Carcinogenesis, 32(10), 1518–1524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Hu, Y., Sun, H., O'Flaherty, J. T., & Edwards, I. J. (2013, January). 15-Lipoxygenase-1-mediated metabolism of docosahexaenoic acid is required for syndecan-1 signaling and apoptosis in prostate cancer cells. Carcinogenesis, 34(1), 176–182.

    Article  CAS  PubMed  Google Scholar 

  168. Ikeguchi, M., Hirooka, Y., & Kaibara, N. (2003, January). Heparanase gene expression and its correlation with spontaneous apoptosis in hepatocytes of cirrhotic liver and carcinoma. European Journal of Cancer, 39(1), 86–90.

    Article  CAS  PubMed  Google Scholar 

  169. Rubinfeld, H., Cohen-Kaplan, V., Nass, D., Ilan, N., Meisel, S., Cohen, Z. R., Hadani, M., Vlodavsky, I., & Shimon, I. (2011, December). Heparanase is highly expressed and regulates proliferation in GH-secreting pituitary tumor cells. Endocrinology, 152(12), 4562–4570.

    Article  CAS  PubMed  Google Scholar 

  170. Cohen, I., Pappo, O., Elkin, M., San, T., Bar-Shavit, R., Hazan, R., Peretz, T., Vlodavsky, I., & Abramovitch, R. (2006, April 1). Heparanase promotes growth, angiogenesis and survival of primary breast tumors. International Journal of Cancer, 118(7), 1609–1617.

    Article  CAS  PubMed  Google Scholar 

  171. Zeng, C., Ke, Z. F., Luo, W. R., Yao, Y. H., Hu, X. R., Jie, W., Yin, J. B., & Sun, S. J. (2013, March). Heparanase overexpression participates in tumor growth of cervical cancer in vitro and in vivo. Medical Oncology, 30(1), 403.

    Article  PubMed  CAS  Google Scholar 

  172. Folkman, J. (2007, April). Angiogenesis: An organizing principle for drug discovery? Nature Reviews. Drug Discovery, 6(4), 273–286.

    Article  CAS  PubMed  Google Scholar 

  173. Götte, M., Kersting, C., Radke, I., Kiesel, L., & Wülfing, P. (2007). An expression signature of syndecan-1 (CD138), E-cadherin and c-met is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ. Breast Cancer Research, 9(1), R8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Maeda, T., Desouky, J., & Friedl, A. (2006, March 2). Syndecan-1 expression by stromal fibroblasts promotes breast carcinoma growth in vivo and stimulates tumor angiogenesis. Oncogene, 25(9), 1408–1412.

    Article  CAS  PubMed  Google Scholar 

  175. Yu, S., Lv, H., Zhang, H., Jiang, Y., Hong, Y., Xia, R., Zhang, Q., Ju, W., Jiang, L., Ou, G., Zhang, J., Wang, S., & Zhang, J. (2017, April 1). Heparanase-1-induced shedding of heparan sulfate from syndecan-1 in hepatocarcinoma cell facilitates lymphatic endothelial cell proliferation via VEGF-C/ERK pathway. Biochemical and Biophysical Research Communications, 485(2), 432–439.

    Article  CAS  PubMed  Google Scholar 

  176. Asuthkar, S., Velpula, K. K., Nalla, A. K., Gogineni, V. R., Gondi, C. S., & Rao, J. S. (2014, April 10). Irradiation-induced angiogenesis is associated with an MMP-9-miR-494-syndecan-1 regulatory loop in medulloblastoma cells. Oncogene, 33(15), 1922–1933.

    Article  CAS  PubMed  Google Scholar 

  177. Ilan, N., Elkin, M., & Vlodavsky, I. (2006). Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. The International Journal of Biochemistry & Cell Biology, 38(12), 2018–2039.

    Article  CAS  Google Scholar 

  178. Jiang, W. G., Sanders, A. J., Katoh, M., Ungefroren, H., Gieseler, F., Prince, M., Thompson, S. K., Zollo, M., Spano, D., Dhawan, P., Sliva, D., Subbarayan, P. R., Sarkar, M., Honoki, K., Fujii, H., Georgakilas, A. G., Amedei, A., Niccolai, E., Amin, A., Ashraf, S. S., Ye, L., Helferich, W. G., Yang, X., Boosani, C. S., Guha, G., Ciriolo, M. R., Aquilano, K., Chen, S., Azmi, A. S., Keith, W. N., Bilsland, A., Bhakta, D., Halicka, D., Nowsheen, S., Pantano, F., & Santini, D. (2015, December). Tissue invasion and metastasis: Molecular, biological and clinical perspectives. Seminars in Cancer Biology, 35(Suppl), S244–S275.

    Article  PubMed  CAS  Google Scholar 

  179. Fujii, T., Shimada, K., Tatsumi, Y., Tanaka, N., Fujimoto, K., & Konishi, N. (2016, September). Syndecan-1 up-regulates microRNA-331-3p and mediates epithelial-to-mesenchymal transition in prostate cancer. Molecular Carcinogenesis, 55(9), 1378–1386.

    Article  CAS  PubMed  Google Scholar 

  180. Hassan, H., Greve, B., Pavao, M. S., Kiesel, L., Ibrahim, S. A., & Götte, M. (2013, May). Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation. The FEBS Journal, 280(10), 2216–2227.

    Article  CAS  PubMed  Google Scholar 

  181. Pasqualon, T., Lue, H., Groening, S., Pruessmeyer, J., Jahr, H., Denecke, B., Bernhagen, J., & Ludwig, A. (2016, April). Cell surface syndecan-1 contributes to binding and function of macrophage migration inhibitory factor (MIF) on epithelial tumor cells. Biochimica et Biophysica Acta, 1863(4), 717–726.

    Article  CAS  PubMed  Google Scholar 

  182. Shteingauz, A., Ilan, N., & Vlodavsky, I. (2014, November). Processing of heparanase is mediated by syndecan-1 cytoplasmic domain and involves syntenin and α-actinin. Cellular and Molecular Life Sciences, 71(22), 4457–4470.

    Article  CAS  PubMed  Google Scholar 

  183. Reiland, J., Sanderson, R. D., Waguespack, M., Barker, S. A., Long, R., Carson, D. D., & Marchetti, D. (2004, February 27). Heparanase degrades syndecan-1 and perlecan heparan sulfate: Functional implications for tumor cell invasion. The Journal of Biological Chemistry, 279(9):8047–8055. Epub 2003 Nov 20.

    Google Scholar 

  184. Barash, U., Cohen-Kaplan, V., Dowek, I., Sanderson, R. D., Ilan, N., & Vlodavsky, I. (2010, October). Proteoglycans in health and disease: New concepts for heparanase function in tumor progression and metastasis. The FEBS Journal, 277(19), 3890–3903.

    Article  CAS  PubMed  Google Scholar 

  185. Yang, Y., Macleod, V., Bendre, M., Huang, Y., Theus, A. M., Miao, H. Q., Kussie, P., Yaccoby, S., Epstein, J., Suva, L. J., Kelly, T., & Sanderson, R. D. (2005, February 1). Heparanase promotes the spontaneous metastasis of myeloma cells to bone. Blood, 105(3), 1303–1309.

    Article  CAS  PubMed  Google Scholar 

  186. Edovitsky, E., Elkin, M., Zcharia, E., Peretz, T., & Vlodavsky, I. (2004, August 18). Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis. Journal of the National Cancer Institute, 96(16), 1219–1230.

    Article  CAS  PubMed  Google Scholar 

  187. Roy, M., & Marchetti, D. (2009, February 1). Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis. Journal of Cellular Biochemistry, 106(2), 200–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Götte, M., & Yip, G. W. (2006, November 1). Heparanase, hyaluronan, and CD44 in cancers: A breast carcinoma perspective. Cancer Research, 66(21), 10233–10237.

    Article  PubMed  Google Scholar 

  189. Bandari, S. K., Purushothaman, A., Ramani, V. C., Brinkley, G. J., Chandrashekar, D. S., Varambally, S., Mobley, J. A., Zhang, Y., Brown, E. E., Vlodavsky, I., & Sanderson, R. D. (2018, January). Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior. Matrix Biology, 65, 104–118.

    Article  CAS  PubMed  Google Scholar 

  190. Yip, G. W., Smollich, M., & Götte, M. (2006, September). Therapeutic value of glycosaminoglycans in cancer. Molecular Cancer Therapeutics, 5(9), 2139–2148.

    Article  CAS  PubMed  Google Scholar 

  191. Schönfeld, K., Herbener, P., Zuber, C., Häder, T., Bernöster, K., Uherek, C., & Schüttrumpf, J. (2018, April 17). Activity of Indatuximab Ravtansine against triple-negative breast Cancer in preclinical tumor models. Pharmaceutical Research, 35(6), 118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Jagannath, S., Chanan-Khan, A., Heffner, L. T., Avigan, D., Zimmerman, T. M., Lonial, S., Lutz, R. J., Engling, A., Uherek, C., Osterroth, F., Ruehle, M., Beelitz, M. A., Niemann, G., Wartenberg-Demand, A., Haeder, T., Anderson, K. C., & Munshi, N. C. (2011). BT062, An antibody-drug conjugate directed against CD138, shows clinical activity in patients with relapsed or relapsed/refractory multiple Myeloma. Blood, 118(21), 305–305.

    Article  Google Scholar 

  193. Zhao, S., Han, Z., Ji, C., An, G., Meng, H., & Yang, L. (2018). The research significance of concomitant use of CAR-CD138-NK and CAR-CD19-NK to target multiple myelomas. European Journal of Inflammation, 16, 2058739218788968.

    CAS  Google Scholar 

  194. Guo, B., Chen, M., Han, Q., Hui, F., Dai, H., Zhang, W., Zhang, Y., Wang, Y., Zhu, H., & Han, W. (2016). CD138-directed adoptive immunotherapy of Chimeric Antigen Receptor (CAR)-modified T cells for multiple myeloma. Journal of Cellular Immunotherapy, 2(1), 28–35.

    Article  Google Scholar 

  195. Mohan, C. D., Hari, S., Preetham, H. D., Rangappa, S., Barash, U., Ilan, N., Nayak, S. C., Gupta, V. K., Basappa, V. I., & Rangappa, K. S. (2019, May 31). Targeting heparanase in cancer: Inhibition by synthetic, chemically modified, and natural compounds. iScience, 15, 360–390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Weissmann, M., Arvatz, G., Horowitz, N., Feld, S., Naroditsky, I., Zhang, Y., Ng, M., Hammond, E., Nevo, E., Vlodavsky, I., & Ilan, N. (2016, January 19). Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis. Proceedings of the National Academy of Sciences of the United States of America, 113(3), 704–709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Cassinelli, G., Favini, E., Dal Bo, L., Tortoreto, M., De Maglie, M., Dagrada, G., Pilotti, S., Zunino, F., Zaffaroni, N., & Lanzi, C. (2016, July 26). Antitumor efficacy of the heparan sulfate mimic roneparstat (SST0001) against sarcoma models involves multi-target inhibition of receptor tyrosine kinases. Oncotarget, 7(30), 47848–47863.

    Article  PubMed  PubMed Central  Google Scholar 

  198. Liu, C. J., Lee, P. H., Lin, D. Y., Wu, C. C., Jeng, L. B., Lin, P. W., Mok, K. T., Lee, W. C., Yeh, H. Z., Ho, M. C., Yang, S. S., Lee, C. C., Yu, M. C., Hu, R. H., Peng, C. Y., Lai, K. L., Chang, S. S., & Chen, P. J. (2009, May). Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: A randomized phase II trial for safety and optimal dosage. Journal of Hepatology, 50(5), 958–968.

    Article  CAS  PubMed  Google Scholar 

  199. Liu, C. J., Chang, J., Lee, P. H., Lin, D. Y., Wu, C. C., Jeng, L. B., Lin, Y. J., Mok, K. T., Lee, W. C., Yeh, H. Z., Ho, M. C., Yang, S. S., Yang, M. D., Yu, M. C., Hu, R. H., Peng, C. Y., Lai, K. L., Chang, S. S., & Chen, P. J. (2014, August 28). Adjuvant heparanase inhibitor PI-88 therapy for hepatocellular carcinoma recurrence. World Journal of Gastroenterology, 20(32), 11384–11393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Galli, M., Chatterjee, M., Grasso, M., Specchia, G., Magen, H., Einsele, H., Celeghini, I., Barbieri, P., Paoletti, D., Pace, S., Sanderson, R. D., Rambaldi, A., & Nagler, A. (2018, October). Phase I study of the heparanase inhibitor roneparstat: An innovative approach for ultiple myeloma therapy. Haematologica, 103(10), e469–e472.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Kim, J. H., & Park, J. (2014, September). Prognostic significance of heme oxygenase-1, S100 calcium-binding protein A4, and syndecan-1 expression in primary non-muscle-invasive bladder cancer. Human Pathology, 45(9), 1830–1838.

    Article  CAS  PubMed  Google Scholar 

  202. Szarvas, T., Reis, H., Kramer, G., Shariat, S. F., Vom Dorp, F., Tschirdewahn, S., et al. (2014, April). Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer. Human Pathology, 45(4), 674–682.

    Article  CAS  PubMed  Google Scholar 

  203. Gohji, K., Okamoto, M., Kitazawa, S., Toyoshima, M., Dong, J., Katsuoka, Y., et al. (2001, October). Heparanase protein and gene expression in bladder cancer. The Journal of Urology, 166(4), 1286–1290.

    Article  CAS  PubMed  Google Scholar 

  204. Shafat, I., Pode, D., Peretz, T., Ilan, N., Vlodavsky, I., & Nisman, B. (2008, February). Clinical significance of urine heparanase in bladder cancer progression. Neoplasia N Y N., 10(2), 125–130.

    Article  CAS  Google Scholar 

  205. Loussouarn, D., Campion, L., Sagan, C., Frenel, J.-S., Dravet, F., Classe, J.-M., et al. (2008, June 17). Prognostic impact of syndecan-1 expression in invasive ductal breast carcinomas. British Journal of Cancer, 98(12), 1993–1998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Nguyen, T. L., Grizzle, W. E., Zhang, K., Hameed, O., Siegal, G. P., & Wei, S. (2013, October). Syndecan-1 overexpression is associated with nonluminal subtypes and poor prognosis in advanced breast cancer. American Journal of Clinical Pathology, 140(4), 468–474.

    Article  PubMed  Google Scholar 

  207. Leivonen, M., Lundin, J., Nordling, S., von Boguslawski, K., & Haglund, C. (2004). Prognostic value of syndecan-1 expression in breast cancer. Oncology, 67(1), 11–18.

    Article  CAS  PubMed  Google Scholar 

  208. Barbareschi, M., Maisonneuve, P., Aldovini, D., Cangi, M. G., Pecciarini, L., Angelo Mauri, F., Veronese, S., Caffo, O., Lucenti, A., Palma, P. D., Galligioni, E., & Doglioni, C. (2003, August 1). High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer, 98(3), 474–483.

    Article  PubMed  Google Scholar 

  209. Baba, F., Swartz, K., van Buren, R., Eickhoff, J., Zhang, Y., Wolberg, W., et al. (2006, July). Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype. Breast Cancer Research and Treatment, 98(1), 91–98.

    Article  CAS  PubMed  Google Scholar 

  210. Vornicova, O., Naroditsky, I., Boyango, I., Shachar, S. S., Mashiach, T., Ilan, N., et al. (2017, December 21). Prognostic significance of heparanase expression in primary and metastatic breast carcinoma. Oncotarget, 9(5), 6238–6244.

    PubMed  PubMed Central  Google Scholar 

  211. Sun, X., Zhang, G., Nian, J., Yu, M., Chen, S., Zhang, Y., et al. (2017, June 27). Elevated heparanase expression is associated with poor prognosis in breast cancer: A study based on systematic review and TCGA data. Oncotarget, 8(26), 43521–43535.

    PubMed  PubMed Central  Google Scholar 

  212. Hashimoto, Y., Skacel, M., & Adams, J. C. (2008, June 30). Association of loss of epithelial syndecan-1 with stage and local metastasis of colorectal adenocarcinomas: An immunohistochemical study of clinically annotated tumors. BMC Cancer, 8, 185.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  213. Kim, S. Y., Choi, E. J., Yun, J. A., Jung, E. S., Oh, S. T., Kim, J. G., et al. (2015). Syndecan-1 expression is associated with tumor size and EGFR expression in colorectal carcinoma: A clinicopathological study of 230 cases. International Journal of Medical Sciences, 12(2), 92–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Lundin, M., Nordling, S., Lundin, J., Isola, J., Wiksten, J.-P., & Haglund, C. (2005). Epithelial syndecan-1 expression is associated with stage and grade in colorectal cancer. Oncology, 68(4–6), 306–313.

    Article  CAS  PubMed  Google Scholar 

  215. Nobuhisa, T., Naomoto, Y., Ohkawa, T., Takaoka, M., Ono, R., Murata, T., et al. (2005, April). Heparanase expression correlates with malignant potential in human colon cancer. Journal of Cancer Research and Clinical Oncology, 131(4), 229–237.

    Article  CAS  PubMed  Google Scholar 

  216. Roh, Y. H., Kim, Y. H., Choi, H. J., Lee, K. E., & Roh, M. S. (2008). Syndecan-1 expression in gallbladder cancer and its prognostic significance. European Surgical Research, 41(2), 245–250.

    Article  CAS  PubMed  Google Scholar 

  217. Wu, W., Pan, C., Yu, H., Gong, H., & Wang, Y. (2008, March). Heparanase expression in gallbladder carcinoma and its correlation to prognosis. Journal of Gastroenterology and Hepatology, 23(3), 491–497.

    Article  PubMed  Google Scholar 

  218. Wiksten, J.-P., Lundin, J., Nordling, S., Kokkola, A., & Haglund, C. (2008, August). Comparison of the prognostic value of a panel of tissue tumor markers and established clinicopathological factors in patients with gastric cancer. Anticancer Research, 28(4C), 2279–2287.

    PubMed  Google Scholar 

  219. Wiksten, J. P., Lundin, J., Nordling, S., Lundin, M., Kokkola, A., von Boguslawski, K., et al. (2001, January 20). Epithelial and stromal syndecan-1 expression as predictor of outcome in patients with gastric cancer. International Journal of Cancer, 95(1), 1–6.

    Article  CAS  PubMed  Google Scholar 

  220. Takaoka, M., Naomoto, Y., Ohkawa, T., Uetsuka, H., Shirakawa, Y., Uno, F., et al. (2003, May). Heparanase expression correlates with invasion and poor prognosis in gastric cancers. Laboratory Investigation; A Journal of Technical Methods and Pathology, 83(5), 613–622.

    Article  CAS  PubMed  Google Scholar 

  221. Inki, P., Joensuu, H., Grénman, R., Klemi, P., & Jalkanen, M. (1994, August). Association between syndecan-1 expression and clinical outcome in squamous cell carcinoma of the head and neck. British Journal of Cancer, 70(2), 319–323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Anttonen, A., Kajanti, M., Heikkilä, P., Jalkanen, M., & Joensuu, H. (1999, February). Syndecan-1 expression has prognostic significance in head and neck carcinoma. British Journal of Cancer, 79(3–4), 558–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Mukunyadzi, P., Liu, K., Hanna, E. Y., Suen, J. Y., & Fan, C.-Y. (2003, August). Induced expression of syndecan-1 in the stroma of head and neck squamous cell carcinoma. Modern Pathology, 16(8), 796–801.

    Article  PubMed  Google Scholar 

  224. Beckhove, P., Helmke, B. M., Ziouta, Y., Bucur, M., Dörner, W., Mogler, C., et al. (2005, April 15). Heparanase expression at the invasion front of human head and neck cancers and correlation with poor prognosis. Clinical Cancer Research, 11(8), 2899–2906.

    Article  CAS  PubMed  Google Scholar 

  225. Gökden, N., Greene, G. F., Bayer-Garner, I. B., Spencer, H. J., Sanderson, R. D., & Gökden, M. (2006, June). Expression of CD138 (Syndecan-1) in renal cell carcinoma is reduced with increasing nuclear grade. Applied Immunohistochemistry & Molecular Morphology, 14(2), 173–177.

    Article  Google Scholar 

  226. Mikami, S., Oya, M., Shimoda, M., Mizuno, R., Ishida, M., Kosaka, T., et al. (2008, October 1). Expression of heparanase in renal cell carcinomas: Implications for tumor invasion and prognosis. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 14(19), 6055–6061.

    Article  CAS  Google Scholar 

  227. Ren, J., Liu, H., Yan, L., Tian, S., Li, D., & Xu, Z. (2011, December 2). Microvessel density and heparanase over-expression in clear cell renal cell cancer: Correlations and prognostic significances. World Journal of Surgical Oncology, 9, 158.

    Article  PubMed  PubMed Central  Google Scholar 

  228. Harada, K., Masuda, S., Hirano, M., & Nakanuma, Y. (2003, September). Reduced expression of syndecan-1 correlates with histologic dedifferentiation, lymph node metastasis, and poor prognosis in intrahepatic cholangiocarcinoma. Human Pathology, 34(9), 857–863.

    Article  CAS  PubMed  Google Scholar 

  229. Nault, J.-C., Guyot, E., Laguillier, C., Chevret, S., Ganne-Carrie, N., N’Kontchou, G., et al. (2013, August). Serum proteoglycans as prognostic biomarkers of hepatocellular carcinoma in patients with alcoholic cirrhosis. Cancer Epidemiology, Biomarkers & Prevention : A Publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 22(8), 1343–1352.

    Article  CAS  Google Scholar 

  230. El-Assal, O. N., Yamanoi, A., Ono, T., Kohno, H., & Nagasue, N. (2001, May). The clinicopathological significance of heparanase and basic fibroblast growth factor expressions in hepatocellular carcinoma. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 7(5), 1299–1305.

    CAS  Google Scholar 

  231. Anttonen, A., Heikkilä, P., Kajanti, M., Jalkanen, M., & Joensuu, H. (2001, June). High syndecan-1 expression is associated with favourable outcome in squamous cell lung carcinoma treated with radical surgery. Lung Cancer, 32(3), 297–305.

    Article  CAS  PubMed  Google Scholar 

  232. Joensuu, H., Anttonen, A., Eriksson, M., Mäkitaro, R., Alfthan, H., Kinnula, V., et al. (2002, September 15). Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer. Cancer Research, 62(18), 5210–5217.

    CAS  PubMed  Google Scholar 

  233. Anttonen, A., Leppä, S., Ruotsalainen, T., Alfthan, H., Mattson, K., & Joensuu, H. (2003, August). Pretreatment serum syndecan-1 levels and outcome in small cell lung cancer patients treated with platinum-based chemotherapy. Lung Cancer, 41(2), 171–177.

    Article  PubMed  Google Scholar 

  234. Cohen, E., Doweck, I., Naroditsky, I., Ben-Izhak, O., Kremer, R., Best, L. A., et al. (2008, September 1). Heparanase is overexpressed in lung cancer and correlates inversely with patient survival. Cancer, 113(5), 1004–1011.

    Article  PubMed  Google Scholar 

  235. Fernandes dos Santos, T. C., Gomes, A. M., Paschoal, M. E. M., Stelling, M. P., Rumjanek, V. M. B. D., Junior A do R, et al. (2014, August). Heparanase expression and localization in different types of human lung cancer. Biochimica et Biophysica Acta, 1840(8), 2599–2608.

    Article  PubMed  CAS  Google Scholar 

  236. Neagu, M., Constantin, C., & Zurac, S. (2013). Immune parameters in the prognosis and therapy monitoring of cutaneous melanoma patients: Experience, role, and limitations. BioMed Research International, 2013, 107940.

    Article  PubMed  PubMed Central  Google Scholar 

  237. Wang, X., Wen, W., Wu, H., Chen, Y., Ren, G., & Guo, W. (2013, June 21). Heparanase expression correlates with poor survival in oral mucosal melanoma. Medical Oncology, 30(3), 633.

    Article  PubMed  CAS  Google Scholar 

  238. Xu, S., Yang, Z., Zhang, J., Jiang, Y., Chen, Y., Li, H., et al. (2014, October 24). Increased levels of β-catenin, LEF-1, and HPA-1 correlate with poor prognosis for Acral melanoma with negative BRAF and NRAS mutation in BRAF exons 11 and 15 and NRAS exons 1 and 2. DNA and Cell Biology, 34(1), 69–77.

    Article  CAS  Google Scholar 

  239. Vornicova, O., Boyango, I., Feld, S., Naroditsky, I., Kazarin, O., Zohar, Y., et al. (2016, October 6). The prognostic significance of heparanase expression in metastatic melanoma. Oncotarget, 7(46), 74678–74685.

    Article  PubMed  PubMed Central  Google Scholar 

  240. Kurokawa, H., Zhang, M., Matsumoto, S., Yamashita, Y., Tanaka, T., Takamori, K., et al. (2006, May). Reduced syndecan-1 expression is correlated with the histological grade of malignancy at the deep invasive front in oral squamous cell carcinoma. Journal of Oral Pathology and Medicine, 35(5), 301–306.

    Article  PubMed  Google Scholar 

  241. Máthé, M., Suba, Z., Németh, Z., Tátrai, P., Füle, T., Borgulya, G., et al. (2006, May). Stromal syndecan-1 expression is an adverse prognostic factor in oral carcinomas. Oral Oncology, 42(5), 493–500.

    Article  PubMed  CAS  Google Scholar 

  242. Leiser, Y., Abu-El-Naaj, I., Sabo, E., Akrish, S., Ilan, N., Ben-Izhak, O., et al. (2011, June). Prognostic value of heparanase expression and cellular localization in oral cancer. Head & Neck, 33(6), 871–877.

    Article  Google Scholar 

  243. Kusumoto, T., Kodama, J., Seki, N., Nakamura, K., Hongo, A., & Hiramatsu, Y. (2010, April). Clinical significance of syndecan-1 and versican expression in human epithelial ovarian cancer. Oncology Reports, 23(4), 917–925.

    CAS  PubMed  Google Scholar 

  244. Davies, E. J., Blackhall, F. H., Shanks, J. H., David, G., McGown, A. T., Swindell, R., et al. (2004, August 1). Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 10(15), 5178–5186.

    Article  CAS  Google Scholar 

  245. Davidson, B., Shafat, I., Risberg, B., & Ilan, N. (2007, February). Trope’ CG, Vlodavsky I, et al. Heparanase expression correlates with poor survival in metastatic ovarian carcinoma. Gynecologic Oncology, 104(2), 311–319.

    Article  CAS  PubMed  Google Scholar 

  246. Juuti, A., Nordling, S., Lundin, J., Louhimo, J., & Haglund, C. (2005). Syndecan-1 expression—a novel prognostic marker in pancreatic cancer. Oncology, 68(2–3), 97–106.

    Article  CAS  PubMed  Google Scholar 

  247. Rohloff, J., Zinke, J., Schoppmeyer, K., Tannapfel, A., Witzigmann, H., Mössner, J., et al. (2002, April 22). Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma. British Journal of Cancer, 86(8), 1270–1275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Quiros, R. M., Rao, G., Plate, J., Harris, J. E., Brunn, G. J., Platt, J. L., Gattuso, P., Prinz, R. A., Xu, X. (2006). Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival. Cancer, 106(3), 532–40.

    Google Scholar 

Download references

Acknowledgement

Work in the authors’ laboratory has been supported by EU H2020 RISE MSCA-2014 project grant number 645756 (GLYCANC) (to MG) and CNPq Sandwich Doctorate (SWE) grant number 290231/2017-5 – SWE (to FCOBT).

Author information

Authors and Affiliations

  1. Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Felipe C. O. B. Teixeira

  2. Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany

    Felipe C. O. B. Teixeira & Martin Götte

Authors
  1. Felipe C. O. B. Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Götte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Götte .

Editor information

Editors and Affiliations

  1. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Israel Vlodavsky

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ralph D. Sanderson

  3. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Neta Ilan

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Teixeira, F.C.O.B., Götte, M. (2020). Involvement of Syndecan-1 and Heparanase in Cancer and Inflammation. In: Vlodavsky, I., Sanderson, R., Ilan, N. (eds) Heparanase. Advances in Experimental Medicine and Biology, vol 1221. Springer, Cham. https://doi.org/10.1007/978-3-030-34521-1_4

Download citation

Publish with us

Policies and ethics

Search

Navigation