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Br J Cancer ; 97(5): 637-45, 2007 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-17667919

RESUMO

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropin-releasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Proteína Ligante Fas/metabolismo , Neoplasias Ovarianas/patologia , Apoptose/imunologia , Western Blotting , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/fisiologia , Proteína Ligante Fas/genética , Proteína Ligante Fas/imunologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/metabolismo , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
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