RESUMO
CSPG4/NG2 is a multifunctional transmembrane protein with limited distribution in adult tissues including articular cartilage. The purpose of this study was to investigate the possible roles of CSPG4/NG2 in chondrosarcomas and to establish whether this molecule may have potential for targeted therapy. Stable knock-down of CSPG4/NG2 in the JJ012 chondrosarcoma cell line by shRNA resulted in decreased cell proliferation and migration as well as a decrease in gene expression of the MMP (matrix metalloproteinase) 3 protease and ADAMTS4 (aggrecanase). Chondrosarcoma cells in which CSPG4/NG2 was knocked down were more sensitive to doxorubicin than wild-type cells. The results indicate that CSPG4/NG2 has roles in regulating chondrosarcoma cell function in relation to growth, spread and resistance to chemotherapy and that anti-CSPG4/NG2 therapies may have potential in the treatment of surgically unresectable chondrosarcoma.
Assuntos
Neoplasias Ósseas/patologia , Proteoglicanas de Sulfatos de Condroitina/fisiologia , Condrossarcoma/patologia , Proteínas de Membrana/fisiologia , Adulto , Idoso , Antineoplásicos/farmacologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Cartilagem Articular/enzimologia , Adesão Celular/fisiologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteoglicanas de Sulfatos de Condroitina/genética , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Condrossarcoma/genética , Condrossarcoma/metabolismo , Docetaxel , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes/métodos , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiologia , Peptídeo Hidrolases/metabolismo , RNA Interferente Pequeno/genética , Taxoides/farmacologia , Adulto JovemRESUMO
Chondrosarcomas are malignant cartilage tumours. They are poorly responsive to chemotherapy and radiotherapy. Treatment is usually limited to surgical resection; however, survival of patients with high-grade chondrosarcoma is poor, even with wide surgical resection. Induction of apoptosis in chondrosarcoma cells, either directly or by enhancement of the response to chemotherapeutic drugs and radiation, may be a route by which outcome can be improved. In this article, we review potential molecular targets that regulate chondrocyte apoptosis and discuss the experimental evidence for their utility.