Journal Article

DKFZ-2023-01131

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Sialic acid metabolism orchestrates transcellular connectivity and signalling in glioblastoma.

Kuliesiute, U. ; Joseph, K. ; Straehle, J. ; Ravi, V. M. ; Kueckelhaus, J. ; Kada Benotmane, J. ; Zhang, J. ; Vlachos, A. ; Beck, J. ; Schnell, O. ; Neniskyte, U. ; Heiland, D. H.DKFZ*

2023
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noad101

Abstract: 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.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.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.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.

Keyword(s): Glioblastoma ; cancer neuroscience ; glioma circuits ; sialic acid ; sialidases

Note: 2023 Nov 2;25(11):1963-1975

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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