The investigation of the glycobiology of dissected glioblastoma human brain tissue

Duration of the project

01.08.2020. - 15.12.2020.

Countries and institutions involved in the project

flag-LT
Life Sciences Center, Vilnius University
flag-DE
Department of Neurosurgery, University of Freiburg

Project Manager

PhD student Ugne Kuliesiute

Project goals

Alterations of cell surface of glycoconjugates, terminal sialic acids in particular, are critical features of many cancers, closely associated with their malignant properties, including invasiveness and metastatic potential. Human glioblastoma cells express very high levels of sialic acids, which have a capacity to reduce cell immunogenicity by masking of cell face antigens. Surface sialylation levels are modulated by enzymes sialidases, of which sialidase Neu3 was found to be downregulated in human glioblastoma specimens, affecting cell invasion and migration, whereas the increased expression and activity of sialidase Neu4 in glioblastoma stem cells showed significant impact on cell survivor. Furthermore, desialylation of microglia was found to increase microglial phagocytosis, indicating that sialylation level may contribute to microglial immunosurveillance within glioblastoma tissue.

However, there is insufficient data on sialidase activity in human glioblastoma tissues. Here, we propose to use a recently developed human organotypic brain slice cultures to investigate the glycobiology of glioblastoma and to identify changes of sialic acid turnover, the expression of sialidases and their enzymatic activity.

This study will help us to understand the causes and the consequences of sialylation changes in glioblastoma for the first time focusing on sialyation as an important component of its malignant properties.

Main activities and venues

The establishment of the partnership, the transfer of state-of-the art human organotypic brain slice culture technique and preliminary data acquisition (University of Freiburg, Department of Neurosurgery, Neurozentrum, Breisacherstr. 64,79108 Freiburg, Germany). The results of this project will be presented in The 12th Conference of The Lithuanian Neuroscience Association and International Conference of Life Sciences The COINS 2021 by oral or poster presentation (Life Sciences Center, Sauletekio av. 7, LT-10257 Vilnius, Lithuania).

Public events

Dr. Vidhya Madapusi Ravi will participate and Dr. Dieter Henrik Heiland, M.D. will participate in The 12th Conference of the Lithuanian Neuroscience Association (November 6, 2020, Life Sciences Center, Lithuania), presenting their research as guest speakers.

Direct and indirect target groups

Direct: PhD student Ugne Kuliesiute and the members of Microenvironment and Immunology Research Laboratory at the University of Freiburg, Department of Neurosurgery, Neurozentrum, Breisacherstr. 64,79108 Freiburg, Germany.

Indirect: This study will gain insights into causes and the consequences of sialylation alterations in glioblastoma. The results will be published and presented in scientific research articles as well as Lithuanian conferences open for the scientific community, expecting the audience of approx. 300 people.

The findings of this study will reveal an important component of malignant properties of glioblastoma with a prospect to design new effective treatments for the patients with glioblastoma that occurs in two to three adults per 100,000 per year world wide.