Characterization of the endolysosomal system in human chordoma cell lines: is there a role of lysosomes in chemoresistance of this rare bone tumor?
Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered a...
| Publicado en: | Histochemistry & Cell Biology Vol. 150; no. 1; pp. 83 - 93 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jul2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=130417452&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 130417452 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09486143 NQI jtl: Histochemistry & Cell Biology issn: 09486143 maglogo: N pubinfo: dt: Jul2018 vid: 150 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 130417452 10.1007/s00418-018-1673-x 130417452 ppf: 83 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Characterization of the endolysosomal system in human chordoma cell lines: is there a role of lysosomes in chemoresistance of this rare bone tumor? aug: au: Kolb-Lenz, Dagmar Fuchs, Robert Lohberger, Birgit Heitzer, Ellen Meditz, Katharina Pernitsch, Dominique Pritz, Elisabeth Groselj-Strele, Andrea Leithner, Andreas Liegl-Atzwanger, Bernadette Rinner, Beate affil: Center of Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010, Graz, Austria sug: ab: Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes. Furthermore, we tested for the first time the cytotoxicity of chloroquine, which targets lysosomes, on chordoma. Cytochemical stainings clearly demonstrated a huge mass of lysosomes in chordoma cell lines with perinuclear accumulation. Also vacuoles in chordoma cells were positive for the lysosomal marker LAMP1 but showed no acidic pH. Genetic analysis detected no apparent mutation associated with known lysosomal pathologies suggesting that vacuolization and the huge lysosomal mass of chordoma cell lines is rather a relict of the notochord than a result of transformation. ELMI investigation of chordoma cells confirmed the presence of large vacuoles, lysosomes and autophagosomes with heterogeneous ultrastructure embedded in glycogen. Interestingly, chordoma cells seem to mobilize cellular glycogen stores via autophagy. Our first preclinical data suggested no therapeutically benefit of chloroquine for chordoma. Even though, chordoma cells are crammed with lysosomes which are according to their discoverer de Duve “cellular suicide bags”. Destabilizing these “suicide bags” might be a promising strategy for the treatment of chordoma. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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