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Involvement of Heparan Sulfate and Heparanase in Neural Development and Pathogenesis of Brain Tumors

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Heparanase

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1221))

Abstract

Brain tumors are aggressive and devastating diseases. The most common type of brain tumor, glioblastoma (GBM), is incurable and has one of the worst five-year survival rates of all human cancers. GBMs are invasive and infiltrate healthy brain tissue, which is one main reason they remain fatal despite resection, since cells that have already migrated away lead to rapid regrowth of the tumor. Curative therapy for medulloblastoma (MB), the most common pediatric brain tumor, has improved, but the outcome is still poor for many patients, and treatment causes long-term complications. Recent advances in the classification of pediatric brain tumors reveal distinct subgroups, allowing more targeted therapy for the most aggressive forms, and sparing children with less malignant tumors the side-effects of massive treatment. Heparan sulfate proteoglycans (HSPGs), main components of the neurogenic niche, interact specifically with a large number of physiologically important molecules and vital roles for HS biosynthesis and degradation in neural stem cell differentiation have been presented. HSPGs are composed of a core protein with attached highly charged, sulfated disaccharide chains. The major enzyme that degrades HS is heparanase (HPSE), an important regulator of extracellular matrix (ECM) remodeling which has been suggested to promote the growth and invasion of other types of tumors. This is of clinical interest because GBM are highly invasive and children with metastatic MB at the time of diagnosis exhibit a worse outcome. Here we review the involvement of HS and HPSE in development of the nervous system and some of its most malignant brain tumors, glioblastoma and medulloblastoma.

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Acknowledgments

This work was supported by grants to K. Forsberg-Nilsson from the Swedish Cancer Society, Swedish Research Council, The Swedish Childhood Cancer Fund and from the European Union’s Horizon 2020 research and innovation program under the Marie Skøodowska-Curie grant agreement No. 645756.

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Authors and Affiliations

  1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Anqi Xiong, Argyris Spyrou & Karin Forsberg-Nilsson

  2. Department of Medical Biochemistry and Biophysics, Karolinska Insitutet, Stockholm, Sweden

    Anqi Xiong

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  1. Anqi Xiong
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  2. Argyris Spyrou
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Correspondence to Karin Forsberg-Nilsson .

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  1. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Israel Vlodavsky

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ralph D. Sanderson

  3. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Neta Ilan

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Xiong, A., Spyrou, A., Forsberg-Nilsson, K. (2020). Involvement of Heparan Sulfate and Heparanase in Neural Development and Pathogenesis of Brain Tumors. In: Vlodavsky, I., Sanderson, R., Ilan, N. (eds) Heparanase. Advances in Experimental Medicine and Biology, vol 1221. Springer, Cham. https://doi.org/10.1007/978-3-030-34521-1_14

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