CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic microenvironment and treatment response

• Autor(a) principal: Trujillo-Paolillo, Alini [UNIFESP]
• Data de Publicação: 2017
• Outros Autores: Tesser-Gamba, Francine [UNIFESP], Petrilli, Antonio Sergio [UNIFESP], de Seixas Alves, Maria Teresa [UNIFESP], Garcia Filho, Reynaldo Jesus [UNIFESP], de Oliveira, Renato [UNIFESP], Caminada de Toledo, Silvia Regina [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/0013000010k6n
• DOI: 10.18632/oncotarget.15869
• Texto Completo: http://dx.doi.org/10.18632/oncotarget.15869; https://repositorio.unifesp.br/handle/11600/53660
• topic: osteosarcoma; cytochrome P-450; osteosarcoma cell line; tumor microenvironment; treatment response

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The present study investigated the expression of Cytochrome P-450 (CYP) genes: CYP1A2, CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post-chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal lung tissues were used as control. We also investigated in five OS cell lines the modulation of CYPs expression by cisplatin, doxorubicin and methotrexate. As result, the adjacent lung specimens presented CYP1A2 overexpression compared to the normal lung (p=0.0256). Biopsy specimens presented lower CYP3A4 expression than normal bone (p=0.0314). The overexpression of both CYP1A2 and CYP3A4 in post-chemotherapy specimens were correlated with better event free-survival (p=0.0244) and good response (p=0.0484), respectively. Furthermore, in vitro assays revealed that CYP1A2 was upregulated by doxorubicin (p=0.0034)