Skip to main content

Advertisement

Log in

Gene expression profiling of human gliomas reveals differences between GBM and LGA related to energy metabolism and notch signaling pathways

  • Original Articles
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Human malignant astrocytic tumors are the most common primary brain malignancies. Human gliomas are classified according to the extent of anaplasia or ‘de-differentiation’ appearance. Although this type of histological classification is widely accepted, the extensive heterogeneity of astrocytic tumors has made their pathological classification rather difficult. New genome-scale high throughput technologies for gene expression profiling, such as DNA microarrays, are emerging as new tools to allow a more accurate identification and characterization of different tumor degrees by discovering new specific markers and pathways of each stage. Present work reports interesting results that might be useful to differentiate between tumor grades. Data presented here provides new evidences about the molecular basis underlying different tumor stages. In this sense, we identified key metabolic pathways, crucial for tumor progression, as being differentially regulated in different tumor stages. On the other hand, remarkable findings regarding Notch pathway are reported, as some members of this receptor family were found to be differentially expressed depending on the malignancy degree. Our results clearly point out important molecular differences between different tumor stages and suggest that more studies are needed to understand specific molecular events characteristic of each stage. These types of studies represent a first step to deepen into the tumor physiology, which may potentially help for better and a more precise diagnosis of gliomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allenspach, E. J., Maillard, I., Aster, J. C., & Pear, W. S. (2002). Notch signaling in cancer. Cancer Biology & Therapy, 1, 466–476.

    Google Scholar 

  • Al-Shahrour, F., Diaz-Uriarte, R., & Dopazo, J. (2004). FatiGO: A web tool for finding significant associations of Gene Ontology terms with groups of genes. Bioinformatics, 20, 578–580.

    Article  PubMed  CAS  Google Scholar 

  • Al-Shahrour, F., Diaz-Uriarte, R., & Dopazo, J. (2005). Discovering molecular functions significantly related to phenotypes by combining gene expression data and biological information. Bioinformatics, 21, 2988–2993.

    Article  PubMed  CAS  Google Scholar 

  • Al-Shahrour, F., Minguez, P., Tarraga, J., Montaner, D., Alloza, E., Vaquerizas, J. M., et al. (2006). BABELOMICS: A systems biology perspective in the functional annotation of genome-scale experiments. Nucleic Acids Research, 34, W472-W476.

    Article  PubMed  CAS  Google Scholar 

  • Brat, D. J., Bellail, A. C., & Van Meir, E. G. (2005). The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neurooncology, 7, 122–133.

    CAS  Google Scholar 

  • Chang, C. Y., Li, M. C., Liao, S. L., Huang, Y. L., Shen, C. C., & Pan, H. C. (2005). Prognostic and clinical implication of IL-6 expression in gliblastoma multiforme. Journal of Clinical Neuroscience, 12, 930–933.

    Article  PubMed  CAS  Google Scholar 

  • Charalambous, C., Pen, L. B., Su, Y. S., Milan, J., Chen, T. C., & Hofman, F. M. (2005). Interleukin-8 differentially regulates migration of tumor-associated and normal human brain endothelial cells. Cancer Research, 65, 10347–10354.

    Article  PubMed  CAS  Google Scholar 

  • Fan, X., Mikolaenko, I., Elhassan, I., Ni, X., Wang, Y., Ball, D., et al. (2004). Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Research, 64, 7787–7793.

    Article  PubMed  CAS  Google Scholar 

  • Fuller, G. N., Rhee, C. H., Hess, K. R., Caskey, L. S., Wang, R., Bruner, J. M., et al. (1999). Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: A revelation by parallel gene expression profiling. Cancer Research, 59, 4228–4232.

    PubMed  CAS  Google Scholar 

  • Gaiano, N., & Fishell, G. (2002). The role of notch in promoting glial and neural stem cell fates. Annual Review of Neuroscience, 25, 471–490.

    Article  PubMed  CAS  Google Scholar 

  • Godard, S., Getz, G., Delorenzi, M., Farmer, P., Kobayashi, H., Desbaillets, I., et al. (2003). Classification of human astrocytic gliomas on the basis of gene expression: A correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Research, 63, 6613–6625.

    PubMed  CAS  Google Scholar 

  • Griguer, C. E., Oliva, C. R., & Gillespie, G. Y. (2005). Glucose metabolism heterogeneity in human and mouse malignant glioma cell lines. Journal of Neuro-oncology, 74, 123–133.

    Article  PubMed  CAS  Google Scholar 

  • Hallahan, A. R., Pritchard, J. I., Hansen, S., Benson, M., Stoeck, J., Hatton, B. A., et al. (2004). The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Research, 64, 7794–7800.

    Article  PubMed  CAS  Google Scholar 

  • Hoelzinger, D. B., Mariani, L., Weis, J., Woyke, T., Berens, T. J., McDonough, W. S., et al. (2005). Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia, 7, 7–16.

    Article  PubMed  CAS  Google Scholar 

  • Huang, H., Colella, S., Kurrer, M., Yonekawa, Y., Kleihues, P., & Ohgaki, H. (2000). Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. Cancer Research, 60, 6868–6874.

    PubMed  CAS  Google Scholar 

  • Kato, K., Ogura, T., Kishimoto, A., Minegishi, Y., Nakajima, N., Miyazaki, M., et al. (2002). Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene, 21, 6082–6090.

    Article  PubMed  CAS  Google Scholar 

  • Larson, D. F., & Horak, K. (2006). Macrophage migration inhibitory factor: Controller of systemic inflammation. Critical Care, 10, 138.

    Article  PubMed  Google Scholar 

  • Lasky, J. L., & Wu, H. (2005). Notch signaling, brain development, and human disease. Pediatric Research, 57, 104R-109R.

    Article  PubMed  Google Scholar 

  • Laurent, N., de Bouard, S., Guillamo, J. S., Christov, C., Zini, R., Jouault, H., et al. (2004). Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo. Molecular Cancer Therapeutics, 3, 129–136.

    PubMed  CAS  Google Scholar 

  • Liang, Q., Xiong, H., Gao, G., Xiong, K., Wang, X., Zhao, Z., et al. (2005a). Inhibition of basigin expression in glioblastoma cell line via antisense RNA reduces tumor cell invasion and angiogenesis. Cancer Biology & Therapy, 4, 759–762.

    Article  CAS  Google Scholar 

  • Liang, Y., Diehn, M., Watson, N., Bollen, A. W., Aldape, K. D., Nicholas, M. K., et al. (2005b). Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme. Proceedings of the National Academy of Sciences of the United States of America, 102, 5814–5819.

    Article  PubMed  CAS  Google Scholar 

  • Mischel, P. S., Cloughesy, T. F., & Nelson, S. F. (2004). DNA-microarray analysis of brain cancer: Molecular classification for therapy. Nature Reviews. Neuroscience, 5, 782–792.

    Article  PubMed  CAS  Google Scholar 

  • Nagashima, G., Suzuki, R., Asai, J. I., Noda, M., Fujimoto, M., & Fujimoto, T. (2003). Tissue reconstruction process in the area of peri-tumoural oedema caused by glioblastoma-immunohistochemical and graphical analysis using brain obtained at autopsy. Acta Neurochirurgica. Supplementum, 86, 507–511.

    CAS  Google Scholar 

  • Nickoloff, B. J., Osborne, B. A., & Miele, L. (2003). Notch signaling as a therapeutic target in cancer: A new approach to the development of cell fate modifying agents. Oncogene, 22, 6598–6608.

    Article  PubMed  CAS  Google Scholar 

  • Phillips, H. S., Kharbanda, S., Chen, R., Forrest, W. F., Soriano, R. H., Wu, T. D., et al. (2006). Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell, 9, 157–173.

    Article  PubMed  CAS  Google Scholar 

  • Radtke, F., & Raj, K. (2003). The role of Notch in tumorigenesis: Oncogene or tumour suppressor? Nature Reviews. Cancer, 3, 756–767.

    Article  PubMed  CAS  Google Scholar 

  • Rich, J. N., Hans, C., Jones, B., Iversen, E. S., McLendon, R. E., Rasheed, B. K., et al. (2005). Gene expression profiling and genetic markers in glioblastoma survival. Cancer Research, 65, 4051–4058.

    Article  PubMed  CAS  Google Scholar 

  • Rickman, D. S., Bobek, M. P., Misek, D. E., Kuick, R., Blaivas, M., Kurnit, D. M., et al. (2001). Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis. Cancer Research, 61, 6885–6891.

    PubMed  CAS  Google Scholar 

  • Rodriguez-Enriquez, S., Vital-Gonzalez, P. A., Flores-Rodriguez, F. L., Marin-Hernandez, A., Ruiz-Azuara, L., & Moreno-Sanchez, R. (2006). Control of cellular proliferation by modulation of oxidative phosphorylation in human and rodent fast-growing tumor cells. Toxicology and Applied Pharmacology, 215(2), 208–217.

    Article  PubMed  CAS  Google Scholar 

  • Sallinen, S. L., Sallinen, P. K., Haapasalo, H. K., Helin, H. J., Helen, P. T., Schraml, P., et al. (2000). Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Research, 60, 6617–6622.

    PubMed  CAS  Google Scholar 

  • Shai, R. M. (2006). Microarray tools for deciphering complex diseases. Frontiers in Bioscience, 11, 1414–1424.

    Article  PubMed  CAS  Google Scholar 

  • Solecki, D. J., Liu, X. L., Tomoda, T., Fang, Y., & Hatten, M. E. (2001). Activated Notch2 signaling inhibits differentiation of cerebellar granule neuron precursors by maintaining proliferation. Neuron, 31, 557–568.

    Article  PubMed  CAS  Google Scholar 

  • Spataro, V., Norbury, C., & Harris, A. L. (1998). The ubiquitin-proteasome pathway in cancer. British Journal of Cancer, 77, 448–455.

    PubMed  CAS  Google Scholar 

  • van den Boom, J., Wolter, M., Kuick, R., Misek, D. E., Youkilis, A. S., Wechsler, D. S., et al. (2003). Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction. American Journal of Pathology, 163, 1033–1043.

    PubMed  Google Scholar 

  • Warburg, O. (1956). On the origin of cancer cells. Science, 123, 309–314.

    Article  PubMed  CAS  Google Scholar 

  • Zhou, Y. H., Hess, K. R., Liu, L., Linskey, M. E., & Yung, W. K. (2005). Modeling prognosis for patients with malignant astrocytic gliomas: Quantifying the expression of multiple genetic markers and clinical variables. Neurooncology, 7, 485–494.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Margareto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Margareto, J., Larrarte, E., Leis, O. et al. Gene expression profiling of human gliomas reveals differences between GBM and LGA related to energy metabolism and notch signaling pathways. J Mol Neurosci 32, 53–63 (2007). https://doi.org/10.1007/s12031-007-0008-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-007-0008-5

Keywords

Navigation