Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
van Oosterwijk, JG; Meijer, D; van Ruler, MA; van den Akker, BE; Oosting, J; Krenács, T; Picci, P; Flanagan, AM; Liegl-Atzwanger, B; Leithner, A; Athanasou, N; Daugaard, S; Hogendoorn, PC; Bovée, JV.
Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFβ as potential targets.
Am J Pathol. 2013; 182(4):1347-1356
Doi: 10.1016/j.ajpath.2012.12.036
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- Co-Autor*innen der Med Uni Graz
- Leithner Andreas
- Liegl-Atzwanger Bernadette
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- Abstract:
- The mesenchymal, clear cell, and dedifferentiated chondrosarcoma subtypes are extremely rare, together constituting 10% to 15% of all chondrosarcomas. Their poor prognosis and lack of efficacious treatment emphasizes the need to elucidate the pathways playing a pivotal role in these tumors. We constructed tissue microarrays containing 42 dedifferentiated, 23 clear cell, and 23 mesenchymal chondrosarcomas and performed immunohistochemistry to study the expression of growth plate-signaling molecules and molecules shown to be involved in conventional chondrosarcoma. We observed high expression of SOX-9 and FGFR-3, as well as aberrant cellular localization of heparan sulfate proteoglycans, in all subtypes. TGFβ signaling through p-SMAD2 and PAI-1 was highly active in all chondrosarcoma subtypes, which suggests that TGFβ inhibitors as a possible therapeutic strategy in rare chondrosarcoma subtypes. As in conventional chondrosarcoma, antiapoptotic proteins (Bcl-2, and/or Bcl-xl) were highly expressed in all subtypes. Inhibition with the BH-3 mimetic ABT-737 rendered dedifferentiated chondrosarcoma cell lines sensitive to doxorubicin or cisplatin. Our data indicate that antiapoptotic proteins may play an important role in chemoresistance, suggesting a promising role for targeting Bcl-2 family members in chondrosarcoma treatment, irrespective of the subtype.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Antineoplastic Agents - pharmacology
- Cell Dedifferentiation - drug effects
- Chondrosarcoma, Mesenchymal - classification
- Drug Resistance, Neoplasm - drug effects
- Female -
- Humans -
- Immunohistochemistry -
- Male -
- Middle Aged -
- Molecular Targeted Therapy -
- Neoplasm Proteins - metabolism
- Paraffin Embedding -
- Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors
- Sarcoma, Clear Cell - classification
- Signal Transduction - drug effects
- Tissue Fixation -
- Transforming Growth Factor beta - antagonists & inhibitors
- Young Adult -