Journal of Neuro-Oncology

, Volume 83, Issue 2, pp 135–144

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

  • Laura Todaro
  • Silvia Christiansen
  • Mirta Varela
  • Paola Campodónico
  • M. Guadalupe Pallotta
  • José Lastiri
  • Eugenia Sacerdote de Lustig
  • Elisa Bal de Kier Joffé
  • Lydia Puricelli
Original Paper

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 (< 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.

Keywords

NCAM Brain tumors Serum marker Tissular marker 

References

  1. 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 13:425–456PubMedCrossRefGoogle Scholar
  2. 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 41:49–64PubMedCrossRefGoogle Scholar
  3. 3.
    Prag S, Lepekhin EA, Kolkova K et al (2002) NCAM regulates cell motility. J Cell Sci 115:283–292PubMedGoogle Scholar
  4. 4.
    Panicker AK, Buhusi M, Thelen K et al (2003) Cellular signalling mechanisms of neural cell adhesion molecules. Front Biosci 8:d900–911PubMedCrossRefGoogle Scholar
  5. 5.
    Gower HJ, Barton CH, Elsom VL et al (1988) Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell 55:955–964PubMedCrossRefGoogle Scholar
  6. 6.
    Goridis C, Brunet JF (1992) NCAM: structural diversity, function and regulation of expression. Semin Cell Biol 3:189–197PubMedCrossRefGoogle Scholar
  7. 7.
    Crossin KL, Chuong CM, Edelman GM (1985) Expression sequences of cell adhesion molecules. Proc Natl Acad Sci USA 82:6942–6946PubMedCrossRefGoogle Scholar
  8. 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 55:99–106PubMedCrossRefGoogle Scholar
  9. 9.
    Hampel H, Korschenhausen DA, Schwarz MJ et al (1997) Detection of the novel cell adhesion molecule MUC18 in human brain tissue. Neuroimmunomodulation 4:57–61PubMedGoogle Scholar
  10. 10.
    Ronn LC, Berezin V, Bock E (2000) The neural cell adhesion molecule in synaptic plasticity and ageing. Int J Dev Neurosci 18:193–199PubMedCrossRefGoogle Scholar
  11. 11.
    Cotman CW, Hailer NP, Pfister KK et al (1998) Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations? Prog Neurobiol 55:659–669PubMedCrossRefGoogle Scholar
  12. 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 74:69–82PubMedCrossRefGoogle Scholar
  13. 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 130:834–843PubMedCrossRefGoogle Scholar
  14. 14.
    Tezel E, Kawase Y, Takeda S et al (2001) Expression of neural cell adhesion molecule in pancreatic cancer. Pancreas 22:122–125PubMedCrossRefGoogle Scholar
  15. 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 82:1921–1931PubMedCrossRefGoogle Scholar
  16. 16.
    Lantuejoul S, Laverriere MH, Sturm N et al (2000) NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas. Hum Pathol 31:415–421PubMedCrossRefGoogle Scholar
  17. 17.
    Gluer S, Schelp C, Madry N et al (1998) Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. Br J Cancer 78:106–110PubMedGoogle Scholar
  18. 18.
    Fogar P, Basso D, Pasquali C et al (1997) Neural cell adhesion molecule (N-CAM) in gastrointestinal neoplasias. Anticancer Res 17:1227–1230PubMedGoogle Scholar
  19. 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 43:680–686PubMedCrossRefGoogle Scholar
  20. 20.
    Lynch DF Jr., Hassen W, Clements MA et al (1997) Serum levels of endothelial and neural cell adhesion molecules in prostate cancer. Prostate 32:214–220PubMedCrossRefGoogle Scholar
  21. 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 129:539–541PubMedCrossRefGoogle Scholar
  22. 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 15:387–393PubMedCrossRefGoogle Scholar
  23. 23.
    Louis DN, Pomeroy SL, Cairncross JG (2002) Focus on central nervous system neoplasia. Cancer Cell 1:125–128PubMedCrossRefGoogle Scholar
  24. 24.
    Demuth T, Berens ME (2004) Molecular mechanisms of glioma cell migration and invasion. J Neurooncol 70:217–228PubMedCrossRefGoogle Scholar
  25. 25.
    Michotte A, Neyns B, Chaskis C et al (2004) Neuropathological and molecular aspects of low-grade and high-grade gliomas. Acta Neurol Belg 104:148–153PubMedGoogle Scholar
  26. 26.
    Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1:44–51PubMedCrossRefGoogle Scholar
  27. 27.
    Ware ML, Berger MS, Binder DK (2003) Molecular biology of glioma tumorigenesis. Histol Histopathol 18:207–216PubMedGoogle Scholar
  28. 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 7:485–494PubMedCrossRefGoogle Scholar
  29. 29.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRefGoogle Scholar
  30. 30.
    Mossman D, Somoza E (1991) ROC curves, test accuracy, and the description of diagnostic tests. J Neuropsychiatry Clin Neurosci 3:330–333PubMedGoogle Scholar
  31. 31.
    Besson A, Yong VW (2001) Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas. J Neurooncol 51:245–264PubMedCrossRefGoogle Scholar
  32. 32.
    Sanson M, Thillet J, Hoang-Xuan K (2004) Molecular changes in gliomas. Curr Opin Oncol 16:607–613PubMedCrossRefGoogle Scholar
  33. 33.
    Wittekind C, Neid M (2005) Cancer invasion and metastasis. Oncology 69(Suppl 1):14–16aPubMedCrossRefGoogle Scholar
  34. 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 11:681–690PubMedCrossRefGoogle Scholar
  35. 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 58:116–122PubMedCrossRefGoogle Scholar
  36. 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 50:6364–6370PubMedGoogle Scholar
  37. 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 17:207–217PubMedGoogle Scholar
  38. 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 22:1267–1276PubMedCrossRefGoogle Scholar
  39. 39.
    Nybroe O, Linnemann D, Bock E (1989) Heterogeneity of soluble neural cell adhesion molecule. J Neurochem 53:1372–1378PubMedCrossRefGoogle Scholar
  40. 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 58:2020–2028PubMedGoogle Scholar
  41. 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 280:38305–38316Google Scholar
  42. 42.
    Suzuki M, Suzuki M, Nakayama J et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15:887–894PubMedCrossRefGoogle Scholar
  43. 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 58:978–980PubMedCrossRefGoogle Scholar
  44. 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 6:4–10PubMedCrossRefGoogle Scholar
  45. 45.
    Kleinschmidt-Demasters BK, Rojiani AM, Filley CM (2006) Central and extrapontine myelinolysis: then ... and now. J Neuropathol Exp Neurol 65:1–11PubMedGoogle Scholar
  46. 46.
    Onodera H, Nagayama S, Tachibana T et al (2005) Brain metastasis from colorectal cancer. Int J Colorectal Dis 20:57–61PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Laura Todaro
    • 1
  • Silvia Christiansen
    • 2
  • Mirta Varela
    • 1
    • 2
  • Paola Campodónico
    • 1
  • M. Guadalupe Pallotta
    • 2
  • José Lastiri
    • 2
  • Eugenia Sacerdote de Lustig
    • 1
    • 2
  • Elisa Bal de Kier Joffé
    • 1
  • Lydia Puricelli
    • 1
  1. 1.Research Area of the Institute of Oncology “Angel H. Roffo”University of Buenos AiresBuenos AiresArgentina
  2. 2.Hospital Italiano de Buenos AiresBuenos AiresArgentina

Personalised recommendations