Histochemistry and Cell Biology

, Volume 150, Issue 1, pp 83–92 | Cite as

Characterization of the endolysosomal system in human chordoma cell lines: is there a role of lysosomes in chemoresistance of this rare bone tumor?

  • Dagmar Kolb-Lenz
  • Robert FuchsEmail author
  • Birgit Lohberger
  • Ellen Heitzer
  • Katharina Meditz
  • Dominique Pernitsch
  • Elisabeth Pritz
  • Andrea Groselj-Strele
  • Andreas Leithner
  • Bernadette Liegl-Atzwanger
  • Beate Rinner
Short Communication


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.


Chordoma Lysosomes Glycogen Glycophagy Chloroquine 



The authors would like to thank Marie-Therese Frisch for her technical assistance. This work was supported by the Medical University of Graz, a grant from the Austrian Science Fund (FWF), P24006 (to RF) and by private donations obtained via a fund-raising campaign kindly initiated by MEFOgraz (to RF). The identity of donors remained completely anonymous for all authors involved, excluding any conflict of interest in this regard. No commercial benefits of any kind have been or will be received from institutions related directly or indirectly to the subject of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

418_2018_1673_MOESM1_ESM.tif (1.8 mb)
Supplementary Figure S1 Chordoma cells are able to perform phagocytosis. Living U-CH2 cells were stained in parallel with Lysotracker® Red and the Hoechst nuclear dye. In the phase contrast view vacuoles (arrow) were visible which showed an acidic pH and contained cellular and nuclear fragments, indicating phagocytotic clearance of dead cells in chordoma cell cultures. Scale bar: 50 μm (TIF 1832 KB)
418_2018_1673_MOESM2_ESM.tif (83 kb)
Supplementary Table 1 Overview of autophagy-lysosomal pathway (ALP) related genes included in mutational analysis. In total 336 ALP-related genes in the chordoma cell lines MUG-CC1 and MUG-Chor1 cell lines were investigated (TIF 83 KB)
418_2018_1673_MOESM3_ESM.tif (184 kb)
Supplementary Table 2 The table shows the summary of results obtained in mutation analysis of genes relevant for the physiology of lysosomes in the MUG-CC1 and MUG-Chor1 cell lines (TIF 184 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Dagmar Kolb-Lenz
    • 1
    • 2
  • Robert Fuchs
    • 3
    Email author
  • Birgit Lohberger
    • 4
  • Ellen Heitzer
    • 5
  • Katharina Meditz
    • 6
  • Dominique Pernitsch
    • 1
  • Elisabeth Pritz
    • 1
  • Andrea Groselj-Strele
    • 1
  • Andreas Leithner
    • 4
  • Bernadette Liegl-Atzwanger
    • 7
  • Beate Rinner
    • 6
  1. 1.Center of Medical ResearchMedical University of GrazGrazAustria
  2. 2.Chair of Cell Biology, Histology and EmbryologyGottfried Schatz Research CenterGrazAustria
  3. 3.Chair of Immunology and Pathophysiology, Otto Loewi Research CenterMedical University of GrazGrazAustria
  4. 4.Department of Orthopaedics and TraumaMedical University of GrazGrazAustria
  5. 5.Diagnostic & Research Institute of Human Genetics, Diagnostic and Research Center for Molecular BiomedicineMedical University of GrazGrazAustria
  6. 6.Division of Biomedical ResearchMedical University of GrazGrazAustria
  7. 7.Diagnostic & Research Institute of Pathology, Diagnostic and Research Center for Molecular BioMedicineMedical University of GrazGrazAustria

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