Skip to main content

Advertisement

SpringerLink
Log in

Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors

  • Original Paper
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The neural cell adhesion molecule (NCAM) is involved in the intercellular junctions of neurons and glial cells. We investigated its relevance as a biomarker in gliomas which main characteristic is their high invasiveness.

We studied by Western blot the pattern of serum NCAM bands in patients with gliomas (n = 34), with brain metastasis of different primary cancers (n = 27) and with benign brain tumors (n = 22)] compared with healthy controls (n = 69). For densitometric analysis NCAM bands ≥130 kDa (HMW) and <130 kDa (LMW) were clustered. We observed that glioma patients presented higher NCAM HMW and lower NCAM LMW levels than control subjects (P < 0.01). A similar pattern was found in patients with brain metastasis or brain benign tumors, suggesting that the pattern of serum NCAM bands would be useful to detect brain tumor pathology. On the other hand, serum NCAM expression was not associated with the main clinicopathological features of gliomas, including overall survival. Interestingly, we found that 9/12 patients with glioma showed a significant decrease in NCAM HMW/LMW ratio between 1–3 months after successful tumor removal. Thus, serum NCAM could be a useful marker for monitoring treatment.

NCAM expression was also analyzed at tissular level in 59 glioma sections from paraffined tumors. We observed that NCAM immunostaining was inversely correlated with the histological grade of malignancy, remaining this association in a multivariate analysis. Besides, loss of NCAM staining was significantly associated with bad prognosis in an univariate analysis.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Walsh FS, Doherty P (1997) Neural cell adhesion molecules of the immunoglobulin superfamily: role in axon growth and guidance. Annu Rev Cell Dev Biol 13:425–456

    Article  PubMed  CAS  Google Scholar 

  2. Burg MA, Halfter W, Cole GJ (1995) Analysis of proteoglycan expression in developing chicken brain: characterization of a heparan sulfate proteoglycan that interacts with the neural cell adhesion molecule. J Neurosci Res 41:49–64

    Article  PubMed  CAS  Google Scholar 

  3. Prag S, Lepekhin EA, Kolkova K et al (2002) NCAM regulates cell motility. J Cell Sci 115:283–292

    PubMed  CAS  Google Scholar 

  4. Panicker AK, Buhusi M, Thelen K et al (2003) Cellular signalling mechanisms of neural cell adhesion molecules. Front Biosci 8:d900–911

    Article  PubMed  CAS  Google Scholar 

  5. Gower HJ, Barton CH, Elsom VL et al (1988) Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell 55:955–964

    Article  PubMed  CAS  Google Scholar 

  6. Goridis C, Brunet JF (1992) NCAM: structural diversity, function and regulation of expression. Semin Cell Biol 3:189–197

    Article  PubMed  CAS  Google Scholar 

  7. Crossin KL, Chuong CM, Edelman GM (1985) Expression sequences of cell adhesion molecules. Proc Natl Acad Sci USA 82:6942–6946

    Article  PubMed  CAS  Google Scholar 

  8. Ni Dhuill CM, Fox GB, Pittock SJ et al (1999) Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age. J Neurosci Res 55:99–106

    Article  PubMed  CAS  Google Scholar 

  9. Hampel H, Korschenhausen DA, Schwarz MJ et al (1997) Detection of the novel cell adhesion molecule MUC18 in human brain tissue. Neuroimmunomodulation 4:57–61

    PubMed  CAS  Google Scholar 

  10. Ronn LC, Berezin V, Bock E (2000) The neural cell adhesion molecule in synaptic plasticity and ageing. Int J Dev Neurosci 18:193–199

    Article  PubMed  CAS  Google Scholar 

  11. Cotman CW, Hailer NP, Pfister KK et al (1998) Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations? Prog Neurobiol 55:659–669

    Article  PubMed  CAS  Google Scholar 

  12. Ricard CS, Pena JD, Hernandez MR (1999) Differential expression of neural cell adhesion molecule isoforms in normal and glaucomatous human optic nerve heads. Brain Res Mol Brain Res 74:69–82

    Article  PubMed  CAS  Google Scholar 

  13. Huerta S, Srivatsan ES, Venkatesan N et al (2001) Alternative mRNA splicing in colon cancer causes loss of expression of neural cell adhesion molecule. Surgery 130:834–843

    Article  PubMed  CAS  Google Scholar 

  14. Tezel E, Kawase Y, Takeda S et al (2001) Expression of neural cell adhesion molecule in pancreatic cancer. Pancreas 22:122–125

    Article  PubMed  CAS  Google Scholar 

  15. Sasaki H, Yoshida K, Ikeda E et al (1998) Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse correlation with malignancy. Cancer 82:1921–1931

    Article  PubMed  CAS  Google Scholar 

  16. Lantuejoul S, Laverriere MH, Sturm N et al (2000) NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas. Hum Pathol 31:415–421

    Article  PubMed  CAS  Google Scholar 

  17. Gluer S, Schelp C, Madry N et al (1998) Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. Br J Cancer 78:106–110

    PubMed  CAS  Google Scholar 

  18. Fogar P, Basso D, Pasquali C et al (1997) Neural cell adhesion molecule (N-CAM) in gastrointestinal neoplasias. Anticancer Res 17:1227–1230

    PubMed  CAS  Google Scholar 

  19. van Kammen DP, Poltorak M, Kelley ME et al (1998) Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia. Biol Psychiatry 43:680–686

    Article  PubMed  Google Scholar 

  20. Lynch DF Jr., Hassen W, Clements MA et al (1997) Serum levels of endothelial and neural cell adhesion molecules in prostate cancer. Prostate 32:214–220

    Article  PubMed  CAS  Google Scholar 

  21. Chang H, Bartlett ES, Patterson B et al (2005) The absence of CD56 on malignant plasma cells in the cerebrospinal fluid is the hallmark of multiple myeloma involving central nervous system. Br J Haematol 129:539–541

    Article  PubMed  Google Scholar 

  22. Todaro L, Puricelli L, Gioseffi H et al (2004) Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type Neurobiol Dis 15:387–393

    Article  PubMed  CAS  Google Scholar 

  23. Louis DN, Pomeroy SL, Cairncross JG (2002) Focus on central nervous system neoplasia. Cancer Cell 1:125–128

    Article  PubMed  CAS  Google Scholar 

  24. Demuth T, Berens ME (2004) Molecular mechanisms of glioma cell migration and invasion. J Neurooncol 70:217–228

    Article  PubMed  Google Scholar 

  25. Michotte A, Neyns B, Chaskis C et al (2004) Neuropathological and molecular aspects of low-grade and high-grade gliomas. Acta Neurol Belg 104:148–153

    PubMed  CAS  Google Scholar 

  26. Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1:44–51

    Article  PubMed  CAS  Google Scholar 

  27. Ware ML, Berger MS, Binder DK (2003) Molecular biology of glioma tumorigenesis. Histol Histopathol 18:207–216

    PubMed  CAS  Google Scholar 

  28. Zhou YH, Hess KR, Liu L et al (2005) Modeling prognosis for patients with malignant astrocytic gliomas: quantifying the expression of multiple genetic markers and clinical variables. Neuro-oncol 7:485–494

    Article  PubMed  CAS  Google Scholar 

  29. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  30. Mossman D, Somoza E (1991) ROC curves, test accuracy, and the description of diagnostic tests. J Neuropsychiatry Clin Neurosci 3:330–333

    PubMed  CAS  Google Scholar 

  31. Besson A, Yong VW (2001) Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas. J Neurooncol 51:245–264

    Article  PubMed  CAS  Google Scholar 

  32. Sanson M, Thillet J, Hoang-Xuan K (2004) Molecular changes in gliomas. Curr Opin Oncol 16:607–613

    Article  PubMed  CAS  Google Scholar 

  33. Wittekind C, Neid M (2005) Cancer invasion and metastasis. Oncology 69(Suppl 1):14–16a

    Article  PubMed  Google Scholar 

  34. Edvardsen K, Brunner N, Spang-Thomsen M et al (1993) Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells. Int J Dev Neurosci 11:681–690

    Article  PubMed  CAS  Google Scholar 

  35. Edvardsen K, Pedersen PH, Bjerkvig R et al (1994) Transfection of glioma cells with the neural-cell adhesion molecule NCAM: effect on glioma-cell invasion and growth in vivo. Int J Cancer 58:116–122

    Article  PubMed  CAS  Google Scholar 

  36. Figarella-Branger DF, Durbec PL, Rougon GN (1990) Differential spectrum of expression of neural cell adhesion molecule isoforms and L1 adhesion molecules on human neuroectodermal tumors. Cancer Res 50:6364–6370

    PubMed  CAS  Google Scholar 

  37. Frost G, Patel K, Bourne S et al (1991) Expression of alternative isoforms of the neural cell adhesion molecule (NCAM) on normal brain and a variety of brain tumours. Neuropathol Appl Neurobiol 17:207–217

    PubMed  CAS  Google Scholar 

  38. Lantuejoul S, Moro D, Michalides RJ et al (1998) Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol 22:1267–1276

    Article  PubMed  CAS  Google Scholar 

  39. Nybroe O, Linnemann D, Bock E (1989) Heterogeneity of soluble neural cell adhesion molecule. J Neurochem 53:1372–1378

    Article  PubMed  CAS  Google Scholar 

  40. Owens GC, Orr EA, DeMasters BK et al (1998) Overexpression of a transmembrane isoform of neural cell adhesion molecule alters the invasiveness of rat CNS-1 glioma. Cancer Res 58:2020–2028

    PubMed  CAS  Google Scholar 

  41. Nakata D and Troy FA, 2nd (2005) Degree of polymerization (DP) of polysialic acid (polySia) on neural cell adhesion molecules (N-CAMS): development and application of a new strategy to accurately determine the DP of polySia chains on N-CAMS. J Biol Chem 280:38305–38316

    Google Scholar 

  42. Suzuki M, Suzuki M, Nakayama J et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15:887–894

    Article  PubMed  CAS  Google Scholar 

  43. Kontogianni K, Nicholson AG, Butcher D et al (2005) CD56: a useful tool for the diagnosis of small cell lung carcinomas on biopsies with extensive crush artefact. J Clin Pathol 58:978–980

    Article  PubMed  CAS  Google Scholar 

  44. Liu J, Zheng S, Yu JK et al (2005) Serum protein fingerprinting coupled with artificial neural network distinguishes glioma from healthy population or brain benign tumor. J Zhejiang Univ Sci B 6:4–10

    Article  PubMed  CAS  Google Scholar 

  45. Kleinschmidt-Demasters BK, Rojiani AM, Filley CM (2006) Central and extrapontine myelinolysis: then ... and now. J Neuropathol Exp Neurol 65:1–11

    PubMed  CAS  Google Scholar 

  46. Onodera H, Nagayama S, Tachibana T et al (2005) Brain metastasis from colorectal cancer. Int J Colorectal Dis 20:57–61

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the following grants: Préstamo BID 1201/OC-AR PICT 4926 and Préstamo BID 1728/OC-AR PICT 11217 (SECYT).

Author information

Authors and Affiliations

  1. Research Area of the Institute of Oncology “Angel H. Roffo”, University of Buenos Aires, Av. San Martin 5481, Buenos Aires, C1417DTB, Argentina

    Laura Todaro, Mirta Varela, Paola Campodónico, Eugenia Sacerdote de Lustig, Elisa Bal de Kier Joffé & Lydia Puricelli

  2. Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Silvia Christiansen, Mirta Varela, M. Guadalupe Pallotta, José Lastiri & Eugenia Sacerdote de Lustig

Authors
  1. Laura Todaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Silvia Christiansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mirta Varela
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paola Campodónico
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Guadalupe Pallotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José Lastiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eugenia Sacerdote de Lustig
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elisa Bal de Kier Joffé
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lydia Puricelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lydia Puricelli.

Additional information

Laura Todaro, Elisa Bal de Kier Joffé and Lydia Puricelli are members of the National Council of Scientific and Technical Research (CONICET).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Todaro, L., Christiansen, S., Varela, M. et al. Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors. J Neurooncol 83, 135–144 (2007). https://doi.org/10.1007/s11060-006-9312-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-006-9312-0

Keywords

Search

Navigation