Polysialic Acid Neural Cell Adhesion Molecule (PSA-NCAM) is an Adverse Prognosis Factor in Glioblastoma, and Regulates Olig2 Expression in Glioma Cell Lines

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2010 Mar 12

PMID 20219118

Citations 53

Authors

Marie-Claude Amoureux

Bema Coulibaly

Olivier Chinot

Anderson Loundou

Philippe Metellus

Genevieve Rougon

Dominique Figarella-Branger

Affiliations

Soon will be listed here.

Abstract

Background: Glioblastoma multiforme (GBM) is the most aggressive and frequent brain tumor, albeit without cure. Although patient survival is limited to one year on average, significant variability in outcome is observed. The assessment of biomarkers is needed to gain better knowledge of this type of tumor, help prognosis, design and evaluate therapies. The neurodevelopmental polysialic acid neural cell adhesion molecule (PSA-NCAM) protein is overexpressed in various cancers. Here, we studied its expression in GBM and evaluated its prognosis value for overall survival (OS) and disease free survival (DFS).

Methods: We set up a specific and sensitive enzyme linked immunosorbent assay (ELISA) test for PSA-NCAM quantification, which correlated well with PSA-NCAM semi quantitative analysis by immunohistochemistry, and thus provides an accurate quantitative measurement of PSA-NCAM content for the 56 GBM biopsies analyzed. For statistics, the Spearman correlation coefficient was used to evaluate the consistency between the immunohistochemistry and ELISA data. Patients' survival was estimated by using the Kaplan-Meier method, and curves were compared using the log-rank test. On multivariate analysis, the effect of potential risk factors on the DFS and OS were evaluated using the cox regression proportional hazard models. The threshold for statistical significance was p = 0.05.

Results: We showed that PSA-NCAM was expressed by approximately two thirds of the GBM at variable levels. On univariate analysis, PSA-NCAM content was an adverse prognosis factor for both OS (p = 0.04) and DFS (p = 0.0017). On multivariate analysis, PSA-NCAM expression was an independent negative predictor of OS (p = 0.046) and DFS (p = 0.007). Furthermore, in glioma cell lines, PSA-NCAM level expression was correlated to the one of olig2, a transcription factor required for gliomagenesis.

Conclusion: PSA-NCAM represents a valuable biomarker for the prognosis of GBM patients.

Citing Articles

Genomic tumor evolution dictates human medulloblastoma progression.

Ruchiy Y, Tsea I, Preka E, Verhoeven B, Olsen T, Mei S Neurooncol Adv. 2024; 6(1):vdae172.

PMID: 39659836 PMC: 11629688. DOI: 10.1093/noajnl/vdae172.

NCAM and attached polysialic acid affect behaviors of breast epithelial cells through differential signaling pathways.

Wu Y, Yang J, Wang X, Guo J, Tan Z, Guan F Acta Biochim Biophys Sin (Shanghai). 2024; .

PMID: 39420834 PMC: 11693866. DOI: 10.3724/abbs.2024176.

Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases.

Wissfeld J, Abou Assale T, Cuevas-Rios G, Liao H, Neumann H Front Neurol. 2024; 15:1330874.

PMID: 38529039 PMC: 10961342. DOI: 10.3389/fneur.2024.1330874.

Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells.

Schildhauer P, Selke P, Staege M, Harder A, Scheller C, Strauss C Cells. 2023; 12(23).

PMID: 38067186 PMC: 10706364. DOI: 10.3390/cells12232758.

Glycocalyx transduces membrane leak in brain tumor cells exposed to sharp magnetic pulsing.

Johns S, Gupta P, Lee Y, Friend J, Fuster M Biophys J. 2023; 122(22):4425-4439.

PMID: 37992690 PMC: 10698326. DOI: 10.1016/j.bpj.2023.10.020.

References

Muller D, Wang C, Skibo G, Toni N, Cremer H, Calaora V . PSA-NCAM is required for activity-induced synaptic plasticity. Neuron. 1996; 17(3):413-22. DOI: 10.1016/s0896-6273(00)80174-9. View

Jaques G, Auerbach B, Pritsch M, Wolf M, Madry N, Havemann K . Evaluation of serum neural cell adhesion molecule as a new tumor marker in small cell lung cancer. Cancer. 1993; 72(2):418-25. DOI: 10.1002/1097-0142(19930715)72:2<418::aid-cncr2820720217>3.0.co;2-q. View

Tanaka F, Otake Y, Nakagawa T, Kawano Y, Miyahara R, Li M . Prognostic significance of polysialic acid expression in resected non-small cell lung cancer. Cancer Res. 2001; 61(4):1666-70. View

Daniel L, Durbec P, Gautherot E, Rouvier E, Rougon G, Figarella-Branger D . A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the role of polysialic acids in the metastatic process. Oncogene. 2001; 20(8):997-1004. DOI: 10.1038/sj.onc.1204176. View

Mahal L, Charter N, Angata K, Fukuda M, Koshland Jr D, Bertozzi C . A small-molecule modulator of poly-alpha 2,8-sialic acid expression on cultured neurons and tumor cells. Science. 2001; 294(5541):380-1. DOI: 10.1126/science.1062192. View

Decker L, Durbec P, Rougon G, Baron-Van Evercooren A . Loss of polysialic residues accelerates CNS neural precursor differentiation in pathological conditions. Mol Cell Neurosci. 2002; 19(2):225-38. DOI: 10.1006/mcne.2001.1072. View

Arellano J, DeFelipe J, Munoz A . PSA-NCAM immunoreactivity in chandelier cell axon terminals of the human temporal cortex. Cereb Cortex. 2002; 12(6):617-24. DOI: 10.1093/cercor/12.6.617. View

Trouillas J, Daniel L, Guigard M, Tong S, Gouvernet J, Jouanneau E . Polysialylated neural cell adhesion molecules expressed in human pituitary tumors and related to extrasellar invasion. J Neurosurg. 2003; 98(5):1084-93. DOI: 10.3171/jns.2003.98.5.1084. View

Figarella-Branger D, Dubois C, Chauvin P, De Victor B, Gentet J, Rougon G . Correlation between polysialic-neural cell adhesion molecule levels in CSF and medulloblastoma outcomes. J Clin Oncol. 1996; 14(7):2066-72. DOI: 10.1200/JCO.1996.14.7.2066. View

10.

Rainov N, Dobberstein K, Bahn H, Holzhausen H, Lautenschlager C, Heidecke V . Prognostic factors in malignant glioma: influence of the overexpression of oncogene and tumor-suppressor gene products on survival. J Neurooncol. 1997; 35(1):13-28. DOI: 10.1023/a:1005841520514. View

11.

Gluer S, Schelp C, von Schweinitz D, Gerardy-Schahn R . Polysialylated neural cell adhesion molecule in childhood rhabdomyosarcoma. Pediatr Res. 1998; 43(1):145-7. DOI: 10.1203/00006450-199801000-00022. View

12.

Hildebrandt H, Becker C, Gluer S, Rosner H, Gerardy-Schahn R, Rahmann H . Polysialic acid on the neural cell adhesion molecule correlates with expression of polysialyltransferases and promotes neuroblastoma cell growth. Cancer Res. 1998; 58(4):779-84. View

13.

Krushel L, Tai M, Cunningham B, Edelman G, Crossin K . Neural cell adhesion molecule (N-CAM) domains and intracellular signaling pathways involved in the inhibition of astrocyte proliferation. Proc Natl Acad Sci U S A. 1998; 95(5):2592-6. PMC: 19425. DOI: 10.1073/pnas.95.5.2592. View

14.

Bruses J, Rutishauser U . Regulation of neural cell adhesion molecule polysialylation: evidence for nontranscriptional control and sensitivity to an intracellular pool of calcium. J Cell Biol. 1998; 140(5):1177-86. PMC: 2132687. DOI: 10.1083/jcb.140.5.1177. View

15.

Whittle I, MacArthur D, Malcolm G, Li M, Washington K, Ironside J . Can experimental models of rodent implantation glioma be improved? A study of pure and mixed glioma cell line tumours. J Neurooncol. 1998; 36(3):231-42. DOI: 10.1023/a:1005831111337. View

16.

Edelman G, Jones F . Gene regulation of cell adhesion: a key step in neural morphogenesis. Brain Res Brain Res Rev. 1998; 26(2-3):337-52. DOI: 10.1016/s0165-0173(97)00034-9. View

17.

Gluer S, Schelp C, Madry N, von Schweinitz D, Eckhardt M, Gerardy-Schahn R . Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma. Br J Cancer. 1998; 78(1):106-10. PMC: 2062928. DOI: 10.1038/bjc.1998.450. View

18.

Singh S, Hawkins C, Clarke I, Squire J, Bayani J, Hide T . Identification of human brain tumour initiating cells. Nature. 2004; 432(7015):396-401. DOI: 10.1038/nature03128. View

19.

Johnson C, Fujimoto I, Rutishauser U, Leckband D . Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion. J Biol Chem. 2004; 280(1):137-45. DOI: 10.1074/jbc.M410216200. View

20.

Fukuda M, Iwadate Y, Machida T, Hiwasa T, Nimura Y, Nagai Y . Cathepsin D is a potential serum marker for poor prognosis in glioma patients. Cancer Res. 2005; 65(12):5190-4. DOI: 10.1158/0008-5472.CAN-04-4134. View