Skip to main content
SpringerLink
Log in

Modulation of proteolytic potential and differentiation by CNTF and BDNF in two mouse neuroblastoma clones: Relation to invasion

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

The effect of CNTF and BDNF on a proteolytic complement instrumental to invasion and on differentiation was studied in two murine neuroblastoma clones, N1 and N7. At the membrane level, gelatinase MMP-2 – mainly the activated form – was restrained by CNTF and BDNF to a residual 34% with both factors; membrane-type 1 MMP was down-regulated to 50% (10 h) and 34% (24 h) with both factors; and urokinase-type plasminogen activator was restrained mainly by BDNF to 70%. In the medium, the two gelatinases MMP-2 and MMP-9 were mainly in zymogen form: only MMP-2 was restrained in N1 cells, while only MMP-9 was restrained in N7 cells by both factors, single or in combination. These effects were paralleled by the induction of neurite outgrowth, which was more stimulated in the less differentiated clone. These dose-dependent and transient effects make CNTF and BDNF ideal candidates for constraining the potentially invasive behavior of nervous system tumors.

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. Parrow V, Nanberg E, Heikkila J et al. Protein kinase C remains functionally active during TPA-induced neuronal differentiation of SH-SY5Y human neuroblastoma cells. J Cell Physiol 1992; 152: 536–44.

    Article  PubMed  CAS  Google Scholar 

  2. Pennypacker KR, Kuhn DM, Billingsley ML. Changes in the expression of tyrosine hydroxylase immunoreactivity in human SMS-KCNR neuroblastoma following retinoic acid or phorbol ester-induced differentiation. Brain Res Mol Brain Res 1989; 5: 251–8.

    Article  PubMed  CAS  Google Scholar 

  3. Bunone G, Borrello MG, Picetti R et al. Induction of RET protooncogene expression in neuroblastoma cells precedes neuronal differentiation and is not mediated by protein synthesis. Exp Cell Res 1995; 217: 92–9.

    Article  PubMed  CAS  Google Scholar 

  4. Chambaut-Guérin A-M, Martinez M-C, Hamimi C et al. Tumor necrosis factor in neuroblastoma SKNBE cells and their regulation by retinoic acid. J Neurochem 1995; 65: 537–44.

    Article  PubMed  Google Scholar 

  5. Menter DG, Herrmann JL, Marchetti D et al. Involvement of neurotrophins and growth factor in brain metastasis formation. Invasion Metastasis 1995; 14: 372–84.

    CAS  Google Scholar 

  6. Snider WD. Functions of the neurotrophins during nervous-system development – what the knockouts are teaching us. Cell 1994; 77: 627–38.

    Article  PubMed  Google Scholar 

  7. Lawrence G, Rylett RJ, Richardson PM et al. Differentiation effects of ciliary neurotrophic factor on human neuroblastoma cells. J Neurochem 1995; 64: 1483–90.

    Article  Google Scholar 

  8. Rossino P, Volpe G, Negro A, et al. Ciliary neurotrhophic factorinduced gene expression in human neuroblastoma cell lines. Neurochem Res 1995; 20: 675–80.

    Article  PubMed  CAS  Google Scholar 

  9. Barletta E, Mugnai G, Ruggieri S. Inverse relationship between invasiveness and differentiative capacity in different human neuroblastoma cell lines. Int J Cancer 1997; 70: 556–60.

    Article  PubMed  CAS  Google Scholar 

  10. Garbisa S, Biggin S, Cavallarin N et al. Tumor invasion: Molecular shears blunted by green tea. Nat Med 1999; 4(11): 1216.

    Article  CAS  Google Scholar 

  11. Ara T, Fukuzawa M, Kusafuka T et al. Immunohistochemical expression of MMP-2, MMP-9, and TIMP-2 in neuroblastoma: Association with tumor progression and clinical outcome. J Pediat Surg 1998; 33: 1272–8.

    Article  PubMed  CAS  Google Scholar 

  12. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 1991; 64: 327–36.

    Article  PubMed  CAS  Google Scholar 

  13. Sato H, Takino T, Okada Y et al. A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 1994; 370: 61–5.

    Article  PubMed  CAS  Google Scholar 

  14. Caenazzo C, Onisto M, Sartor L et al. Augmented membrane type 1 matrix metalloproteinase (MT1-MMP): MMP-2 messenger RNA ratio in gastric carcinomas with poor prognosis. Clin Cancer Res 1998; 4: 2179–86.

    PubMed  CAS  Google Scholar 

  15. Baramova EN, Bajou K, Remacle A et al. Involvement of PA/plasmin system in the processing of pro-MMP-9 and in the second step of pro-MMP-2 activation. FEBS Lett 1997; 405: 157–62.

    Article  PubMed  CAS  Google Scholar 

  16. Mazzieri R, Masiero L, Zanetta L et al. Control of type IV collagenase activity by components of the urokinase-plasmin system: A regulatory mechanism with cell-bound reactants. EMBO J 1997; 16: 101–4.

    Article  Google Scholar 

  17. Negro A, Onisto M, Pellati D et al. CNTF up-regulation of TIMP-2 in neuroblastoma cells. Mol Brain Res 1997; 48: 30–6.

    Article  PubMed  CAS  Google Scholar 

  18. Sidell N, Altman A, Haussler MR et al. Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines. Exp Cell Res 1983; 148: 21–30.

    Article  PubMed  CAS  Google Scholar 

  19. Chambaut-Guérin A-M, Hérigault S, Rouet-Benzineb P et al. Induction of matrix metalloproteinase MMP-9 (92-kDa gelatinase) by retinoic acid in human neuroblastoma SKNBE cells: Relevance to neuronal differentiation. J Neurochem 2000; 74: 508–17.

    Article  PubMed  Google Scholar 

  20. Sugiura Y, Shimada H, Seeger RC et al. Matrix metalloproteinases-2 and-9 are expressed in human neuroblastoma: Contribution of stromal cells to their production and correlation with metastasis. Cancer Res 1998; 58: 2209–16.

    PubMed  CAS  Google Scholar 

  21. Barletta E, Mugnai G, Ruggieri S. Platelet activating factor inhibits the expression of matrix metalloproteinases and affects invasiveness and differentiation in a system of human neuroblastoma clones. Biol Chem 2002; 383: 189–97.

    Article  PubMed  CAS  Google Scholar 

  22. Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J 1982; 1: 549–53.

    PubMed  CAS  Google Scholar 

  23. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001; 24: 677–736.

    Article  PubMed  CAS  Google Scholar 

  24. Bravo J, Heath JK. Receptor recognition by gp130 cytokines. EMBO J 2000; 19: 2399–411.

    Article  PubMed  CAS  Google Scholar 

  25. Arcangeli A, Becchetti A, Mannini A et al. Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels. J Cell Biol 1993; 122: 1131–43.

    Article  PubMed  CAS  Google Scholar 

  26. Negro A, Tolosano E, Skaper SD et al. Cloning and expression of human ciliary neurotrophic factor. Eur J Biochem 1991; 201: 289–94.

    Article  PubMed  CAS  Google Scholar 

  27. Kleiner DE, Stetler-Stevenson WG. Quantitative zymography: Detection of picogram quantities of gelatinases. Anal Biochem 1994; 218: 325–9.

    Article  PubMed  CAS  Google Scholar 

  28. Unemori EN, Hibbs MS, Amento EP. (1991). Constitutive expression of a 92-kD gelatinase (type V collagenase) by rheumatoid synovial fibroblasts and its induction in normal human fibroblasts by inflammatory cytokines. J Clin Invest 1991; 88: 1656–62.

    Article  PubMed  CAS  Google Scholar 

  29. Heinicke E, Kumar U, Munoz DG. Quantitative dot-blot assay for proteins using enhanced chemiluminescence. J Immunol Meth 1992; 152: 227–36.

    Article  CAS  Google Scholar 

  30. Fibbi G, Barletta E, Dini G et al. Cell invasion is affected by differential expression of the urokinase plasminogen activator/urokinase plasminogen receptor system in muscle satellite cells from normal and dystrophic patients. Lab Invest 2001; 81: 27–39.

    PubMed  CAS  Google Scholar 

  31. Quattrone A, Papucci L, Santini V et al. Quantitation of bcl-2 oncogene in cultured lymphoma/leukemia cell lines and in primary leukemia B-cells by a highly sensitive RT-PCR method. Haematologica 1995; 80: 495–504.

    PubMed  CAS  Google Scholar 

  32. Itoh T, Tanioka M, Matsuda H et al. Experimental metastasis is suppressed in MMP-9-deficient mice. Clin Exp Metastasis 1999; 17: 177–81.

    Article  PubMed  CAS  Google Scholar 

  33. Yamamoto M, Mohanam S, Sawaya R et al. Differential expression of membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivo and in vitro. Cancer Res 1996; 56: 384–92.

    PubMed  CAS  Google Scholar 

  34. Lardot C, Delos M, Lison D. Upregulation of urokinase in alveolar macrophages and lung tissue in response to silica particles. Am J Physiol 1998; 274: L1040–8.

    PubMed  CAS  Google Scholar 

  35. Kherif S, Lafuma C, Dehaupas M et al. Expression of matrix metalloproteinases 2 and 9 in regenerating skeletal muscle: A study in experimentally injured and mdx muscles. Dev Biol 1999; 205: 158–70.

    Article  PubMed  CAS  Google Scholar 

  36. Planchenault T, Costa S, Fages C et al. Differential expression of laminin and fibronectin and of their related metalloproteinases in human glioma cell lines: Relation to invasion. Neurosc Lett 2001; 299: 140–4.

    Article  CAS  Google Scholar 

  37. Annabi B, Lachambre MP, Bousquet-Gagnon N et al. Green tea polyphenol (-)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells. Biochim Biophys Acta 2002; 1542: 209–20.

    Article  PubMed  CAS  Google Scholar 

  38. De Chiara TM, Vejsada R, Poueymirou WT et al. (1995) Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth. Cell 1995; 83: 313–22.

    Article  CAS  Google Scholar 

  39. De Veas RG, Schweigerer L, Medina MA. Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in paediatric tumour cells. Effects of tumour cell proliferation modulators on gelatinolytic activity. J Cancer Res Clin Oncol 1995; 121: 275–8.

    Article  PubMed  CAS  Google Scholar 

  40. Fowler C, Zimmer C, Boghaert E et al. Metastasis of C1300 and TBJ murine neuroblastomas correlates with expression of matrix metalloproteinases. Cancer Lett 1995; 93: 171–7.

    Article  PubMed  CAS  Google Scholar 

  41. Quaranta V. Cell migration through extracellular matrix: Membranetype metalloproteinases make the way. J. Cell Biol 2000; 149: 1167–70.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Biomedical Sciences, Medical School of Padova, Padova, Italy

    Luigi Sartor & Spiridione Garbisa

  2. Department of Biological Chemistry, Veterinary School of Padova, Padova, Italy

    Alessandro Negro

  3. Department of Experimental Pathology and Oncology, Medical School of Florence, Florence, Italy

    Emanuela Barletta & Gabriele Mugnai

Authors
  1. Luigi Sartor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandro Negro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emanuela Barletta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriele Mugnai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Spiridione Garbisa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Spiridione Garbisa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sartor, L., Negro, A., Barletta, E. et al. Modulation of proteolytic potential and differentiation by CNTF and BDNF in two mouse neuroblastoma clones: Relation to invasion. Clin Exp Metastasis 19, 709–716 (2002). https://doi.org/10.1023/A:1021302802297

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021302802297

Search

Navigation