Skip to main content

Advertisement

SpringerLink
Log in

Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-κB in upregulation of syndecan-1 expression

  • Laboratory Investigation - human/animal tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

Invasion of tumor cells into the surrounding normal brain tissues is a prominent feature of malignant gliomas. Malignant glioma cells secrete thrombospondin-1 which participates in the motility of glioma cells and binds cell surface heparan sulfate proteoglycan. To clarify the invasion mechanism of tumor cells, expression of the syndecans (syndecan-1, -2, -3, and -4), a major cell surface heparan sulfate proteoglycan family, was analyzed in malignant gliomas. Involvement of nuclear factor-kappaB (NF-κB) on syndecan-1 expression was also investigated. Using reverse transcription-PCR, the authors analyzed the expression of syndecan-1, -2, -3, and -4 in 10 malignant glioma cell lines, 2 glioblastoma specimens, and 2 normal brain specimens. All malignant glioma cell lines and glioblastoma specimens expressed all types of syndecan mRNA, except in one glioma cell line that lacked syndecan-3 expression. On the other hand, normal brain specimens expressed syndecan-2, -3, and -4 mRNA, but did not syndecan-1 mRNA. Syndecan-1 protein was localized in the cell surface of all malignant glioma cell lines by flow cytometry. Various levels of active nuclear factor-kappa B (NF-κB) was detected in all malignant glioma cell lines using immunoblotting. The expression of active NF-κB and syndecan-1 increased in U251 glioma cells after tumor necrosis factor-α or interleukin-1β treatment, which can activate NF-κB. The amplification of active NF-κB and syndecan-1 by tumor necrosis factor-α or interleukin-1β was suppressed by an inhibitor of NF-κB activation (emodin). Emodin also downregulated the expression of syndecan-1 mRNA in U251 cells. These results indicate that malignant glioma cells express all types of syndecans and suggest that NF-κB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with extracellular matrices including thrombospondin-1.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Giese A, Kluwe L, Laube B, Meissner H, Berens ME, Westphal M 1996 Migration of human glioma cells on myelinNeurosurgery 38: 755–764

    Article  PubMed  CAS  Google Scholar 

  2. Naganuma H, Satoh E, Asahara T, Amagasaki K, Watanabe A, Satoh H, Kuroda K, Zhang L, Nukui H 2004 Quantification of thrombospondin-1 secretion and expression of αvβ3 and α3β1 integrins and syndecan-1 as cell-surface receptors for thrombospondin-1 in malignant glioma cellsJ Neurooncol 70: 309–317

    Article  PubMed  Google Scholar 

  3. Kawataki T, Naganuma H, Sasaki A, Yoshikawa H, Tasaka K, Nukui H 2000 Correlation of thrombospondin-1 and transforming growth factor-β expression with malignancy of gliomaNeuropathology 20: 161–169

    Article  PubMed  CAS  Google Scholar 

  4. Amagasaki K, Sasaki A, Kato G, Maeda S, Nukui H, Naganuma H 2001 Antisense-mediated reduction in thrombospondin-1 expression reduces cell motility in malignant glioma cellsInt J Cancer 94: 508–512

    Article  PubMed  CAS  Google Scholar 

  5. Roberts DD 1996 Regulation of tumor growth and metastasis by thrombospondin-1FASEB J 10: 1183–1191

    PubMed  CAS  Google Scholar 

  6. Steck PA, Moser RP, Bruner JM, Liang L, Freidman AN, Hwang TL, Yung WK 1989 Altered expression and distribution of heparan sulfate proteoglycans in human gliomasCancer Res 49: 2096–2103

    PubMed  CAS  Google Scholar 

  7. Adams JC, Kureishy N, Taylor AL 2001 A role for syndecan-1 in coupling fascin spike formation by thrombospondin-1J Cell Biol 152: 1169–1182

    Article  PubMed  CAS  Google Scholar 

  8. Carey DJ 1997 Syndecans: multifunctional cell-surface co-receptorsBiochem J 327: 1–16

    PubMed  CAS  Google Scholar 

  9. Woods A, Couchman JR 1998 Syndecans: synergistic activators of cell adhesionTrends Cell Biol 8: 189–192

    Article  PubMed  CAS  Google Scholar 

  10. Kim W, Goldberger OA, Gallo RL, Bernfield M 1994 Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patternsMol Biol Cell 5: 797–805

    PubMed  CAS  Google Scholar 

  11. Nagai S, Washiyama K, Kurimoto M, Takaku A, Endo S, Kumanishi T 2002 Aberrant nuclear factor-κB activity and its participation in the growth of human malignant astrocytomaJ Neurosurg 96: 909–917

    Article  PubMed  CAS  Google Scholar 

  12. Elenius K, Maatta A, Salmivirta M, Jalkanen M 1992 Growth factors induce 3T3 cells to express bFGF-binding syndecanJ Biol Chem 267: 6435–6441

    PubMed  CAS  Google Scholar 

  13. Worapamorn W, Haase HR, Li H, Bartold PM 2001 Growth factors and cytokines modulate gene expression of cell-surface proteoglycans in human periodontal ligament cellsJ Cell Physiol 186: 448–456

    Article  PubMed  CAS  Google Scholar 

  14. Zhang L, Yamane T, Satoh E, Amagasaki K, Kawataki T, Asahara T, Furuya K, Nukui H, Naganuma H 2005 Establishment and partial characterization of five malignant glioma cell linesNeuropathology 25: 136–143

    Article  PubMed  Google Scholar 

  15. Toyoshima E, Ohsaki Y, Nishigaki Y, Fujimoto Y, Kohgo Y, Kikuchi K 2001 Expression of syndecan-1 is common in human lung cancers independent of expression of epidermal growth factor receptorLung Cancer 31: 193–202

    Article  PubMed  CAS  Google Scholar 

  16. Jalkanen M, Rapraeger A, Saunders S, Bernfield M 1987 Cell surface proteoglycan of mouse mammary epithelial cells is shed by cleavage of its matrix-binding ectodomain from its membrane-associated domainJ Cell Biol 105: 3087–3096

    Article  PubMed  CAS  Google Scholar 

  17. Rapraeger AC, 2001 Molecular interactions of syndecans during development Semin Cell Dev Biol 12: 107–116

    Article  PubMed  CAS  Google Scholar 

  18. Barnes PJ, Karin M, 1997 Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseasesN Engl J Med 336: 1066–1071

    Article  PubMed  CAS  Google Scholar 

  19. Kumar A, Dhawan S, Aggarwal BB, 1998 Emodin (3-methyl-1,6,8-trihydroxy- anthraquinone) inhibits TNF-induced NF-κB activation, IκB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells Oncogene 17: 913–918

    Article  PubMed  CAS  Google Scholar 

  20. Carey DJ, Bendt KM, Stahl RC 1996 The cytoplasmic domain of syndecan-1 is required for cytoskeleton association but not detergent insolubility. Identification of essential cytoplasmic domain residuesJ Biol Chem 271: 15253–15260

    Article  PubMed  CAS  Google Scholar 

  21. Lebakken CS, Rapraeger AC, 1996 Syndecan-1 mediates cell spreading in transfected human lymphoblastoid (Raji) cellsJ Cell Biol 132: 1209–1221

    Article  PubMed  CAS  Google Scholar 

  22. Hinkes MT, Goldberger OA, Neumann PE, Kokenyesi R, Bernfield M, 1993 Organization and promoter activity of the mouse syndecan-1 geneJ Biol Chem 268: 11440–11448

    PubMed  CAS  Google Scholar 

  23. Karin M, Cao Y, Greten FR, Li ZW, 2002 NF-κB in cancer: From innocent bystander to major culpritNat Rev Cancer 2: 301–310

    Article  PubMed  CAS  Google Scholar 

  24. Kabrun N, Enrietto PJ, 1994 The Rel family of proteins in oncogenesis and differentiationSemin Cancer Biol 5: 103–112

    PubMed  CAS  Google Scholar 

  25. Baldwin AS, 2001 Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κBJ Clin Invest 107: 241–246

    Article  PubMed  CAS  Google Scholar 

  26. Takahashi JA, Mori H, Fukumoto M, Igarashi K, Jaye M, Oda Y, Kikuchi H, Hatanaka M, 1990 Gene expression of fibroblast growth factors in human gliomas and meningiomas: demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissuesProc Natl Acad Sci USA 87: 5710–5714

    PubMed  CAS  ADS  Google Scholar 

  27. Sasaki A, Naganuma H, Satoh E, Kawataki T, Amagasaki K, Nukui H, 2001 Participation of thrombospondin-1 in the activation of latent transforming growth factor-β in malignant glioma cellsNeurol Med Chir (Tokyo) 41: 253–259

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Yamanashi, Faculty of Medicine, 409 3898, Nakakoma-gun, Yamanashi, Japan

    Arata Watanabe, Eiji Satoh, Koro Furuya, Lei Zhang & Hirofumi Naganuma

  2. Department of Biochemistry, University of Yamanashi, Faculty of Medicine, 409 3898, Nakakoma-gun, Yamanashi, Japan

    Tadashi Mabuchi & Shuichiro Maeda

  3. Department of Neurosurgery, University of Yamanashi, Faculty of Medicine, 1110 Shimokato, Tamaho-cho, 409 3898, Nakakoma-gun, Yamanashi, Japan

    Hirofumi Naganuma

Authors
  1. Arata Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tadashi Mabuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eiji Satoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koro Furuya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuichiro Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hirofumi Naganuma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hirofumi Naganuma.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Watanabe, A., Mabuchi, T., Satoh, E. et al. Expression of syndecans, a heparan sulfate proteoglycan, in malignant gliomas: participation of nuclear factor-κB in upregulation of syndecan-1 expression. J Neurooncol 77, 25–32 (2006). https://doi.org/10.1007/s11060-005-9010-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-005-9010-3

Keywords

Search

Navigation