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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.03.2011 | Original Paper

Neural cell adhesion molecule isoform 140 declines with rise of WHO grade in human gliomas and serves as indicator for the invasion zone of multiform glioblastomas and brain metastases

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2011

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Abstract

Purpose

Gliomas are highly invasive neuroepithelial tumors with a propensity of malignant transformation and very restricted treatment options. The neural cell adhesion molecule (NCAM) modulates cellular migration, proliferation, and synaptic plasticity by homophilic and heterophilic interactions. Hereby, we investigated its relevance as a glioma tissue marker for the biological aggressiveness of these tumors and compared these features with the carcinoma brain metastasis invasion zone.

Materials and methods

We analyzed 194 human brain samples. Human tumor-free brain specimens served as control for the white and gray matter. In addition to that, we used human glioblastomas from nude rats. All tissues were investigated immunohistochemically for the expression of the NCAM isoform 140. Additionally, the multiplanar MRI-CT fusion neuronavigation-guided serial stereotactic biopsy was performed and completed by histopathological workup.

Results

Human gliomas loose NCAM-140 with the rise of their WHO grade. Meningiomas are NCAM-140 negative. As the most striking feature, human brain metastases and the majority of human glioblastomas of our patients and of nude rats were totally NCAM-140 negative. This NCAM negativity led us to the conclusion of three different main glioblastoma invasion patterns. Surprisingly, the majority of brain metastasis samples that contained surrounding brain parenchyma demonstrated invasive tumor cell nests beyond the sharply demarcated metastasis border. We also found invasive metastatic cell nests outside the contrast enhancing tumor zone by means of the MRI-CT fusion neuronavigation-guided serial stereotactic biopsy.

Conclusion

The expression of NCAM-140 inversely correlates with the WHO grade of human gliomas. The lost expression of NCAM-140 in human glioblastomas and in brain metastases enables the investigation of the brain–tumor interface and the definition of glioblastoma invasion patterns and shows that brain metastases are more invasive than ever thought.

Bussolati B, Grange C, Bruno S, Buttiglieri S, Deregibus MC, Tei L, Aime S, Camussi G (2006) Neural-cell adhesion molecule (NCAM) expression by immature and tumor-derived endothelial cells favors cell organization into capillary-like structures. Exp Cell Res 312(6):913–924CrossRefPubMed

Cavallaro U, Christofori G (2004) Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann N Y Acad Sci 1014:58–66CrossRefPubMed

Chang H, Bartlett ES, Patterson B, Chen CI, Yi QL (2005) The absence of CD56 in malignant plasma cells in the cerebrospinal fluid is the hallmark of multiple myeloma involving central nervous system. B J Haematol 129(4):539–541CrossRef

Cole GJ, Glaser L (1986) A heparin-binding domain from N-CAM is involved in neural cell-substratum adhesion. J Cell Biol 102(2):403–412CrossRefPubMed

Crossin KL, Krushel LA (2000) Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamily. Dev Dyn 218(2):260–279CrossRefPubMed

DiFiglia M, Marshall P, Covault J, Yamamoto M (1989) Ultrastructural localization of molecular subtypes of immunoreactive neural cell adhesion molecule (NCAM) in the adult rodent striatum. J Neurosci 9(12):4158–4168PubMed

Doherty P, Fruns M, Seaton P, Dickson G, Barton CH, Sears TA, Walsh FS (1990) A threshold effect of the major isoforms of NCAM on neurite outgrowth. Nature 343(6257):464–466CrossRefPubMed

Edvardsen K, Brunner N, Spang-Thomsen M, Walsh FS, Bock E (1993a) Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells. Int J Dev Neurosci 11(5):681–690CrossRefPubMed

Edvardsen K, Chen W, Rucklidge G, Walsh FS, Obrink B, Bock E (1993b) Transmembrane neural cell-adhesion molecule (NCAM), but not glycosyl-phosphatidylinositol-anchored NCAM, down-regulates secretion of matrix metalloproteinases. Proc Natl Acad Sci USA 90(24):11463–11467CrossRefPubMed

Engebraaten O, Hjortland GO, Hirschberg H, Fodstad O (1999) Growth of precultured human glioma specimens in nude rat brain. J Neurosurg 90:125–132CrossRefPubMed

Fearon ER, Pierceall WE (1995) The deleted in colorectal cancer (DCC) gene: a candidate tumour suppressor gene encoding a cell surface protein with similarity to neural cell adhesion molecules. Cancer Surv 24:3–17PubMed

Feng Z, Li L, Yong Ng P, Porter AG (2002) Neuronal Differentiation and Protection from Nitric Oxide-Induced Apoptosis Require c-Jun-Dependent Expression of NCAM140. Mol Cell Biol 22(15):5357–5366CrossRefPubMed

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(19):6364–6370PubMed

Figarella-Branger D, Dubois C, Chauvin P, De Victor B, Gentet JC, Rougon G (1996) Correlation between polysialic-neural cell adhesion molecule levels in CSF and medulloblastoma outcomes. J Clin Oncol 14(7):2066–2072PubMed

Figarella-Branger D, Roche PH, Daniel L, Dufour H, Bianco N, Pellissier JF (1997) Cell-adhesion molecules in human meningiomas: correlation with clinical and morphological data. Neuropathol Appl Neurobiol 23(2):113–122CrossRefPubMed

Fogar P, Basso D, Pasquali C, De Paoli M, Sperti C, Roveroni G, Pedrazzoli S, Plebani M (1997) Neural cell adhesion molecule (N-CAM) in gastrointestinal neoplasias. Anticancer Res 17(2B):1227–1230PubMed

Gratsa A, Rooprai HK, Rogers JP, Martin KK, Pilkington GJ (1997) Correlation of expression of NCAM and GD3 ganglioside to motile behaviour in neoplastic glia. Anticancer Res 17(6B):4111–4117PubMed

Hatten ME (1987) Neuronal inhibition of astroglial cell proliferation is membrane mediated. J Cell Biol 104(5):1353–1360CrossRefPubMed

Huang CX, Hu SX, Chen B (2001) Expression of the neural cell adhesion molecule in human astrocytomas. Hunan Yi Ke Da Xue Xue Bao 26(6):543–545PubMed

Hundemer M, Klein U, Hose D, Raab MS, Cremer FW, Jauch A, Benner A, Heiss C, Moos M, Ho AD, Goldschmidt H (2007) Lack of CD56 expression on myeloma cells is not a marker for poor prognosis in patients treated by high-dose chemotherapy and is associated with translocation t(11;14). Bone Marrow Tansplant 40(11):1033–1037CrossRef

Kiss JZ, Muller D (2001) Contribution of the neural cell adhesion molecule to neuronal and synaptic plasticity. Rev Neurosci 12(4):297–310PubMed

Kleinschmidt-DeMasters BK, Orr EA, Savelieva E, Owens GC, Kruse CA (1999) Paucity of retinoic acid receptor alpha (RAR alpha) nuclear immunostaining in gliomas and inability of retinoic acid to influence neural cell adhesion molecule (NCAM) expression. J Neurooncol 41(1):31–42CrossRefPubMed

Krushel LA, Sporns O, Cunningham BA, Crossin KL, Edelman GM (1995) Neural cell adhesion molecule (N-CAM) inhibits astrocyte proliferation after injury to different regions of the adult rat brain. Proc Natl Acad Sci USA 92(10):4323–4327CrossRefPubMed

Krushel LA, Tai MH, Cunningham BA, Edelman GM, Crossin KL (1998) Neural cell adhesion molecule (N-CAM) domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation. Proc Natl Acad Sci USA 95(5):2592–2596CrossRefPubMed

Kuhn SA, Romeike B, Walter J, Kalff R, Reichart R (2009) Multiplanar MRI-CT fusion neuronavigation-guided serial stereotactic biopsy of human brain tumors: proof of a strong correlation between tumor imaging and histopathology by a new technical approach. J Cancer Res Clin Oncol 135(9):1293–1302CrossRefPubMed

Lantuejoul S, Moro D, Michalides RJ, Brambilla C, Brambilla E (1998) Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol 22(10):1267–1276CrossRefPubMed

Maidment SL, Rucklidge GJ, Rooprai HK, Pilkington GJ (1997) An inverse correlation between expression of NCAM-A and the matrix-metalloproteinases gelatinase-A and gelatinase-B in human glioma cells in vitro. Cancer Lett 116(1):71–77CrossRefPubMed

Owens GC, Edelman GM, Cunningham BA (1987) Organization of the neural cell adhesion molecule (N-CAM) gene: alternative exon usage as the basis for different membrane-associated domains. Proc Natl Acad Sci USA 84(1):294–298CrossRefPubMed

Patel K, Frost G, Kiely F, Phimister E, Coakham HB, Kemshead JT (1991) Expression of the cluster 1 antigen (neural cell adhesion molecule) in neuroectodermal tumours. Br J Cancer Suppl 14:20–23PubMed

Prag S, Lepekhin EA, Kolkova K, Hartmann-Petersen R, Kawa A, Walmod PS, Belman V, Gallagher HC, Berezin V, Bock E, Pedersen N (2002) NCAM regulates cell motility. J Cell Sci 115(Pt 2):283–292PubMed

Roesler J, Srivatsan E, Moatamed F, Peters J, Livingston EH (1997) Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma. Am J Surg 174(3):251–257CrossRefPubMed

Rønn LC, Hartz BP, Bock E (1998) The neural cell adhesion molecule (NCAM) in development and plasticity of the nervous system. Exp Gerontol 33(7–8):853–864CrossRefPubMed

Sasaki H, Yoshida K, Ikeda E, Asou H, Inaba M, Otani M, Kawase T (1998) Expression of the neural cell adhesion molecule in astrocytic tumors: an inverse correlation with malignancy. Cancer 82(10):1921–1931CrossRefPubMed

Sporns O, Edelmann GM, Crossin KL (1995) The neural cell adhesion molecule (N-CAM) inhibits proliferation in primary cultures of rat astrocytes. Proc Natl Acad Sci 92:542–546CrossRefPubMed

Storms SD, Rutishauser U (1998) A role for polysialic acid in neural cell adhesion molecule heterophilic binding to proteoglycans. J Biol Chem 273(42):27124–27129CrossRefPubMed

Tews DS, Nissen A (1998) Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors. Invasion Metastasis 18(5–6):271–284CrossRefPubMed

Todaro L, Christiansen S, Varela M, Campodonico P, Pallotta MG, Lastiri J, Sacerdote de Lustig E, Bal de Kier Joffe E, Puricelli L (2007) Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in patients with brain tumors. J Neurooncol 83(2):135–144CrossRefPubMed

Trouillas J, Daniel L, Guigard MP, Tong S, Gouvernet J, Jouanneau E, Jan M, Perrin G, Fischer G, Tabarin A, Rougon G, Figarella-Branger D (2003) Polysialylated neural cell adhesion molecules expresses in human pituitary tumors and related to extrasellar invasion. J Neurosurg 98(5):1084–1093CrossRefPubMed

Walmod PS, Kolkova K, Berezin V, Bock E (2004) Zippers make signals: NCAM-mediated molecular interactions and signal transduction. Neurochem Res 29(11):2015–2035CrossRefPubMed

Titel: Neural cell adhesion molecule isoform 140 declines with rise of WHO grade in human gliomas and serves as indicator for the invasion zone of multiform glioblastomas and brain metastases
Publikationsdatum: 01.03.2011
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2011
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0888-6

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Neural cell adhesion molecule isoform 140 declines with rise of WHO grade in human gliomas and serves as indicator for the invasion zone of multiform glioblastomas and brain metastases

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Purpose

Materials and methods

Results

Conclusion

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