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SHR Neuro Krebs Kardio Lipid

Kolb, D; Pritz, E; Steinecker-Frohnwieser, B; Lohberger, B; Deutsch, A; Kroneis, T; El-Heliebi, A; Dohr, G; Meditz, K; Wagner, K; Koefeler, H; Leitinger, G; Leithner, A; Liegl-Atzwanger, B; Zweytick, D; Rinner, B.
Extended ultrastructural characterization of chordoma cells: the link to new therapeutic options.
PLoS One. 2014; 9(12):e114251-e114251 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Deutsch Alexander
Dohr Gottfried
El-Heliebi Amin
Köfeler Harald
Kolb-Lenz Dagmar
Kroneis Thomas
Leithner Andreas
Leitinger Gerd
Liegl-Atzwanger Bernadette
Lohberger Birgit
Meditz Katharina
Pritz Elisabeth
Rinner Beate
Steinecker-Frohnwieser Bibiane
Wagner Karin
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Number of Figures: 9
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Abstract:
Chordomas are rare bone tumors, developed from the notochord and largely resistant to chemotherapy. A special feature of this tumor is the heterogeneity of its cells. By combining high pressure freezing (HPF) with electron tomography we were able to illustrate the connections within the cells, the cell-cell interface, and the mitochondria-associated endoplasmic reticulum membrane complex that appears to play a special role among the characteristics of chordoma. These lipid raft-like regions are responsible for lipid syntheses and for calcium signaling. Compared to other tumor cells, chordoma cells show a close connection of rough endoplasmic reticulum and mitochondria, which may influence the sphingolipid metabolism and calcium release. We quantified levels of ceramide and glycosylceramide species by the methyl tert-butyl ether extraction method and we assessed the intracellular calcium concentration with the ratiometric fluorescent dye Fura-2AM. Measurements of the changes in the intracellular calcium concentration revealed an increase in calcium due to the application of acetylcholine. With regard to lipid synthesis, glucosylceramide levels in the chordoma cell line were significantly higher than those in normal healthy cells. The accumulation of glycosylceramide in drug resistant cancer cells has been confirmed in many types of cancer and may also account for drug resistance in chordoma. This study aimed to provide a deep morphological description of chordoma cells, it demonstrated that HPF analysis is useful in elucidating detailed structural information. Furthermore we demonstrate how an accumulation of glycosylceramide in chordoma provides links to drug resistance and opens up the field for new research options.
Find related publications in this database (using NLM MeSH Indexing)
Bone Neoplasms - pathology
Cell Line, Tumor -
Chordoma - pathology
Drug Resistance, Neoplasm - genetics
Endoplasmic Reticulum, Rough - metabolism
Humans -
Mitochondria - metabolism
Notochord - metabolism
Sphingolipids - metabolism

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