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Glioblastoma: Role of Galectin-1 in Chemoresistance

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Book cover Tumors of the Central Nervous System, Volume 2

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 2))

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Abstract

Malignant gliomas, especially glioblastomas, are associated with a poor prognosis. This prognosis can be at least partly explained by the fact that glioma cells diffusely infiltrate the brain parenchyma and exhibit decreased levels of apoptosis and are thus resistant to cytotoxic drugs. Galectin-1, the expression of which is stimulated by hypoxia, is a potent modulator of glioblastoma cell migration and a pro-angiogenic molecule. Galectin-1 participates in the resistance of cancer cells, including glioma cells, to chemotherapy and to radiotherapy and is involved in the activation of the Ras oncogenic pathway. Our recent data reveal that temozolomide, the standard treatment for glioma patients, increases Galectin-1 expression in various glioblastoma models both in vitro and in vivo. Consequently, reducing Galectin-1 expression in these models increases the anti-tumor effects of various chemotherapeutic agents, in particular temozolomide. Reducing Galectin-1 expression in glioblastoma cells does not induce apoptotic or autophagic features, but rather modulates p53 transcriptional activity and decreases p53-targeted gene expression. The decrease in Galectin-1 expression also impairs the expression levels of several genes implicated in chemoresistance: ORP150, HERP, GRP78/Bip, TRA1, BNIP3L, GADD45B and CYR61. The involvement of Galectin-1 in different steps of glioma malignant progression, such as migration, angiogenesis or chemoresistance, makes it a potential target for the development of new drugs to combat these malignant tumors.

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Acknowledgments

F. Lefranc is a clinical research fellow and R. Kiss a director of research with the Belgian National FNRS (Belgium). The present chapter was supported by grants awarded by the Fonds de la Recherche Scientifique Médicale (FRSM, Belgium) and by the Fonds Yvonne Boël (Brussels, Belgium).

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  1. Laboratoire de Toxicologie, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), 1050, Brussels, Belgium

    Florence Lefranc & Robert Kiss

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  1. Florence Lefranc
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  2. Robert Kiss
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Correspondence to Florence Lefranc .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Lefranc, F., Kiss, R. (2011). Glioblastoma: Role of Galectin-1 in Chemoresistance. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 2. Tumors of the Central Nervous System, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0618-7_27

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  • DOI: https://doi.org/10.1007/978-94-007-0618-7_27

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