Sialic acid metabolism orchestrates transcellular connectivity and signaling in glioblastoma
Kuliesiute U, Joseph K, Straehle J, Ravi VM, Kueckelhaus J, Benotmane JK, Zhang J, Vlachos A, Beck J, Schnell O, Neniskyte U, Heiland DH (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 25
Pages Range: 1963-1975
Journal Issue: 11
Abstract
Background. In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored.The terminal moiety of cell coating glycans, sialic acid, is of paramount importance for cell-cell contacts. However, sialic acid turnover in gliomas and its impact on tumor networks remain unknown. Methods. We streamlined an experimental setup using organotypic human brain slice cultures as a framework for exploring brain glycobiology, including metabolic labeling of sialic acid moieties and quantification of glycocalyx changes. By live, 2-photon and high-resolution microscopy we have examined morphological and functional effects of altered sialic acid metabolism in GBM. By calcium imaging we investigated the effects of the altered glycocalyx on a functional level of GBM networks. Results. The visualization and quantitative analysis of newly synthesized sialic acids revealed a high rate of de novo sialylation in GBM cells. Sialyltrasferases and sialidases were highly expressed in GBM, indicating that significant turnover of sialic acids is involved in GBM pathology. Inhibition of either sialic acid biosynthesis or desialylation affected the pattern of tumor growth and lead to the alterations in the connectivity of glioblastoma cells network. Conclusions. Our results indicate that sialic acid is essential for the establishment of GBM tumor and its cellular network. They highlight the importance of sialic acid for glioblastoma pathology and suggest that dynamics of sialylation have the potential to be targeted therapeutically.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Freiburg
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Vilnius University / Vilniaus universitetas
Lithuania (LT)
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Vilnius University / Vilniaus universitetas
Lithuania (LT)
How to cite
APA:
Kuliesiute, U., Joseph, K., Straehle, J., Ravi, V.M., Kueckelhaus, J., Benotmane, J.K.,... Heiland, D.H. (2023). Sialic acid metabolism orchestrates transcellular connectivity and signaling in glioblastoma. Neuro-Oncology, 25(11), 1963-1975. https://doi.org/10.1093/neuonc/noad101
MLA:
Kuliesiute, Ugne, et al. "Sialic acid metabolism orchestrates transcellular connectivity and signaling in glioblastoma." Neuro-Oncology 25.11 (2023): 1963-1975.
BibTeX: Download