Skip to main content
Top
Published in: Journal of Neuro-Oncology 2/2007

01-06-2007 | Original Paper

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

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

Published in: Journal of Neuro-Oncology | Issue 2/2007

Login to get access

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.
Literature
1.
go back to reference Walsh FS, Doherty P (1997) Neural cell adhesion molecules of the immunoglobulin superfamily: role in axon growth and guidance. Annu Rev Cell Dev Biol 13:425–456PubMedCrossRef Walsh FS, Doherty P (1997) Neural cell adhesion molecules of the immunoglobulin superfamily: role in axon growth and guidance. Annu Rev Cell Dev Biol 13:425–456PubMedCrossRef
2.
go back to reference 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 41:49–64PubMedCrossRef 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 41:49–64PubMedCrossRef
3.
go back to reference Prag S, Lepekhin EA, Kolkova K et al (2002) NCAM regulates cell motility. J Cell Sci 115:283–292PubMed Prag S, Lepekhin EA, Kolkova K et al (2002) NCAM regulates cell motility. J Cell Sci 115:283–292PubMed
4.
go back to reference Panicker AK, Buhusi M, Thelen K et al (2003) Cellular signalling mechanisms of neural cell adhesion molecules. Front Biosci 8:d900–911PubMedCrossRef Panicker AK, Buhusi M, Thelen K et al (2003) Cellular signalling mechanisms of neural cell adhesion molecules. Front Biosci 8:d900–911PubMedCrossRef
5.
go back to reference Gower HJ, Barton CH, Elsom VL et al (1988) Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell 55:955–964PubMedCrossRef Gower HJ, Barton CH, Elsom VL et al (1988) Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell 55:955–964PubMedCrossRef
6.
go back to reference Goridis C, Brunet JF (1992) NCAM: structural diversity, function and regulation of expression. Semin Cell Biol 3:189–197PubMedCrossRef Goridis C, Brunet JF (1992) NCAM: structural diversity, function and regulation of expression. Semin Cell Biol 3:189–197PubMedCrossRef
7.
go back to reference Crossin KL, Chuong CM, Edelman GM (1985) Expression sequences of cell adhesion molecules. Proc Natl Acad Sci USA 82:6942–6946PubMedCrossRef Crossin KL, Chuong CM, Edelman GM (1985) Expression sequences of cell adhesion molecules. Proc Natl Acad Sci USA 82:6942–6946PubMedCrossRef
8.
go back to reference 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 55:99–106PubMedCrossRef 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 55:99–106PubMedCrossRef
9.
go back to reference Hampel H, Korschenhausen DA, Schwarz MJ et al (1997) Detection of the novel cell adhesion molecule MUC18 in human brain tissue. Neuroimmunomodulation 4:57–61PubMed Hampel H, Korschenhausen DA, Schwarz MJ et al (1997) Detection of the novel cell adhesion molecule MUC18 in human brain tissue. Neuroimmunomodulation 4:57–61PubMed
10.
go back to reference Ronn LC, Berezin V, Bock E (2000) The neural cell adhesion molecule in synaptic plasticity and ageing. Int J Dev Neurosci 18:193–199PubMedCrossRef Ronn LC, Berezin V, Bock E (2000) The neural cell adhesion molecule in synaptic plasticity and ageing. Int J Dev Neurosci 18:193–199PubMedCrossRef
11.
go back to reference Cotman CW, Hailer NP, Pfister KK et al (1998) Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations? Prog Neurobiol 55:659–669PubMedCrossRef Cotman CW, Hailer NP, Pfister KK et al (1998) Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations? Prog Neurobiol 55:659–669PubMedCrossRef
12.
go back to reference 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 74:69–82PubMedCrossRef 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 74:69–82PubMedCrossRef
13.
go back to reference 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 130:834–843PubMedCrossRef 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 130:834–843PubMedCrossRef
14.
go back to reference Tezel E, Kawase Y, Takeda S et al (2001) Expression of neural cell adhesion molecule in pancreatic cancer. Pancreas 22:122–125PubMedCrossRef Tezel E, Kawase Y, Takeda S et al (2001) Expression of neural cell adhesion molecule in pancreatic cancer. Pancreas 22:122–125PubMedCrossRef
15.
go back to reference 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 82:1921–1931PubMedCrossRef 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 82:1921–1931PubMedCrossRef
16.
go back to reference Lantuejoul S, Laverriere MH, Sturm N et al (2000) NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas. Hum Pathol 31:415–421PubMedCrossRef Lantuejoul S, Laverriere MH, Sturm N et al (2000) NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas. Hum Pathol 31:415–421PubMedCrossRef
17.
go back to reference Gluer S, Schelp C, Madry N et al (1998) Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. Br J Cancer 78:106–110PubMed Gluer S, Schelp C, Madry N et al (1998) Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. Br J Cancer 78:106–110PubMed
18.
go back to reference Fogar P, Basso D, Pasquali C et al (1997) Neural cell adhesion molecule (N-CAM) in gastrointestinal neoplasias. Anticancer Res 17:1227–1230PubMed Fogar P, Basso D, Pasquali C et al (1997) Neural cell adhesion molecule (N-CAM) in gastrointestinal neoplasias. Anticancer Res 17:1227–1230PubMed
19.
go back to reference van Kammen DP, Poltorak M, Kelley ME et al (1998) Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia. Biol Psychiatry 43:680–686PubMedCrossRef van Kammen DP, Poltorak M, Kelley ME et al (1998) Further studies of elevated cerebrospinal fluid neuronal cell adhesion molecule in schizophrenia. Biol Psychiatry 43:680–686PubMedCrossRef
20.
go back to reference Lynch DF Jr., Hassen W, Clements MA et al (1997) Serum levels of endothelial and neural cell adhesion molecules in prostate cancer. Prostate 32:214–220PubMedCrossRef Lynch DF Jr., Hassen W, Clements MA et al (1997) Serum levels of endothelial and neural cell adhesion molecules in prostate cancer. Prostate 32:214–220PubMedCrossRef
21.
go back to reference 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 129:539–541PubMedCrossRef 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 129:539–541PubMedCrossRef
22.
go back to reference 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 15:387–393PubMedCrossRef 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 15:387–393PubMedCrossRef
23.
go back to reference Louis DN, Pomeroy SL, Cairncross JG (2002) Focus on central nervous system neoplasia. Cancer Cell 1:125–128PubMedCrossRef Louis DN, Pomeroy SL, Cairncross JG (2002) Focus on central nervous system neoplasia. Cancer Cell 1:125–128PubMedCrossRef
24.
go back to reference Demuth T, Berens ME (2004) Molecular mechanisms of glioma cell migration and invasion. J Neurooncol 70:217–228PubMedCrossRef Demuth T, Berens ME (2004) Molecular mechanisms of glioma cell migration and invasion. J Neurooncol 70:217–228PubMedCrossRef
25.
go back to reference Michotte A, Neyns B, Chaskis C et al (2004) Neuropathological and molecular aspects of low-grade and high-grade gliomas. Acta Neurol Belg 104:148–153PubMed Michotte A, Neyns B, Chaskis C et al (2004) Neuropathological and molecular aspects of low-grade and high-grade gliomas. Acta Neurol Belg 104:148–153PubMed
26.
go back to reference Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1:44–51PubMedCrossRef Kleihues P, Ohgaki H (1999) Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro-oncol 1:44–51PubMedCrossRef
27.
go back to reference Ware ML, Berger MS, Binder DK (2003) Molecular biology of glioma tumorigenesis. Histol Histopathol 18:207–216PubMed Ware ML, Berger MS, Binder DK (2003) Molecular biology of glioma tumorigenesis. Histol Histopathol 18:207–216PubMed
28.
go back to reference 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 7:485–494PubMedCrossRef 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 7:485–494PubMedCrossRef
29.
go back to reference Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRef Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRef
30.
go back to reference Mossman D, Somoza E (1991) ROC curves, test accuracy, and the description of diagnostic tests. J Neuropsychiatry Clin Neurosci 3:330–333PubMed Mossman D, Somoza E (1991) ROC curves, test accuracy, and the description of diagnostic tests. J Neuropsychiatry Clin Neurosci 3:330–333PubMed
31.
go back to reference Besson A, Yong VW (2001) Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas. J Neurooncol 51:245–264PubMedCrossRef Besson A, Yong VW (2001) Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas. J Neurooncol 51:245–264PubMedCrossRef
32.
go back to reference Sanson M, Thillet J, Hoang-Xuan K (2004) Molecular changes in gliomas. Curr Opin Oncol 16:607–613PubMedCrossRef Sanson M, Thillet J, Hoang-Xuan K (2004) Molecular changes in gliomas. Curr Opin Oncol 16:607–613PubMedCrossRef
33.
34.
go back to reference 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 11:681–690PubMedCrossRef 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 11:681–690PubMedCrossRef
35.
go back to reference 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 58:116–122PubMedCrossRef 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 58:116–122PubMedCrossRef
36.
go back to reference 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 50:6364–6370PubMed 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 50:6364–6370PubMed
37.
go back to reference 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 17:207–217PubMed 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 17:207–217PubMed
38.
go back to reference 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 22:1267–1276PubMedCrossRef 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 22:1267–1276PubMedCrossRef
39.
go back to reference Nybroe O, Linnemann D, Bock E (1989) Heterogeneity of soluble neural cell adhesion molecule. J Neurochem 53:1372–1378PubMedCrossRef Nybroe O, Linnemann D, Bock E (1989) Heterogeneity of soluble neural cell adhesion molecule. J Neurochem 53:1372–1378PubMedCrossRef
40.
go back to reference 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 58:2020–2028PubMed 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 58:2020–2028PubMed
41.
go back to reference 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 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
42.
go back to reference Suzuki M, Suzuki M, Nakayama J et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15:887–894PubMedCrossRef Suzuki M, Suzuki M, Nakayama J et al (2005) Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15:887–894PubMedCrossRef
43.
go back to reference 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 58:978–980PubMedCrossRef 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 58:978–980PubMedCrossRef
44.
go back to reference 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 6:4–10PubMedCrossRef 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 6:4–10PubMedCrossRef
45.
go back to reference Kleinschmidt-Demasters BK, Rojiani AM, Filley CM (2006) Central and extrapontine myelinolysis: then ... and now. J Neuropathol Exp Neurol 65:1–11PubMed Kleinschmidt-Demasters BK, Rojiani AM, Filley CM (2006) Central and extrapontine myelinolysis: then ... and now. J Neuropathol Exp Neurol 65:1–11PubMed
46.
go back to reference Onodera H, Nagayama S, Tachibana T et al (2005) Brain metastasis from colorectal cancer. Int J Colorectal Dis 20:57–61PubMedCrossRef Onodera H, Nagayama S, Tachibana T et al (2005) Brain metastasis from colorectal cancer. Int J Colorectal Dis 20:57–61PubMedCrossRef
Metadata
Title
Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors
Authors
Laura Todaro
Silvia Christiansen
Mirta Varela
Paola Campodónico
M. Guadalupe Pallotta
José Lastiri
Eugenia Sacerdote de Lustig
Elisa Bal de Kier Joffé
Lydia Puricelli
Publication date
01-06-2007
Published in
Journal of Neuro-Oncology / Issue 2/2007
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-006-9312-0

Other articles of this Issue 2/2007

Journal of Neuro-Oncology 2/2007 Go to the issue