Screening for potential targets for therapy in mesenchymal, clear cell, and dedifferentiated chondrosarcoma reveals Bcl-2 family members and TGFß as potential targets.
Am J Pathol
; 182(4): 1347-56, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23415961
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. TGFß signaling through p-SMAD2 and PAI-1 was highly active in all chondrosarcoma subtypes, which suggests that TGFß 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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Cuidados_paliativos
/
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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Sarcoma de Células Claras
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Condrossarcoma Mesenquimal
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Proteínas Proto-Oncogênicas c-bcl-2
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Desdiferenciação Celular
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Terapia de Alvo Molecular
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Pathol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Holanda