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@ARTICLE{Kuliesiute:276750,
      author       = {U. Kuliesiute and K. Joseph and J. Straehle and V. M. Ravi
                      and J. Kueckelhaus and J. Kada Benotmane and J. Zhang and A.
                      Vlachos and J. Beck and O. Schnell and U. Neniskyte and D.
                      H. Heiland$^*$},
      title        = {{S}ialic acid metabolism orchestrates transcellular
                      connectivity and signalling in glioblastoma.},
      journal      = {Neuro-Oncology},
      volume       = {25},
      number       = {11},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-01131},
      pages        = {1963-1975},
      year         = {2023},
      note         = {2023 Nov 2;25(11):1963-1975},
      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.},
      keywords     = {Glioblastoma (Other) / cancer neuroscience (Other) / glioma
                      circuits (Other) / sialic acid (Other) / sialidases (Other)},
      cin          = {FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37288604},
      doi          = {10.1093/neuonc/noad101},
      url          = {https://inrepo02.dkfz.de/record/276750},
}