Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation
Copyright policy )Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation
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.
Corticotropin-Releasing Hormone, Messenger rna, Messenger, Apoptosis, Cancer staging, Ovarian neoplasms, Fas ligand, Cancer growth, Corticotropin-Releasing Hormone/genetics/*metabolism/physiology, Receptors, Immune privilege, Regulatory mechanism, Up-regulation, Lymphocytes, Fluorescent Antibody Technique, Indirect, Reverse transcriptase polymerase chain reaction, Cell proliferation, Priority journal, Gene expression regulation, Corticotropin releasing factor, Ovarian Neoplasms, Tumor, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Caspases/metabolism, Receptors, Corticotropin-Releasing Hormone/genetics/metabolism, Correlation analysis, Lymphocytes/cytology/immunology/metabolism, Immunohistochemistry, Up-Regulation, Gene Expression Regulation, Neoplastic, Peripheral lymphocyte, Fluorescent antibody technique, Crh, Caspases, Ovarian Neoplasms/genetics/metabolism/*pathology, Female, Western, Apoptosis/immunology, Human, Corticotropin-releasing hormone, Indirect, Fas Ligand Protein, Ovary cancer, RNA, Messenger/genetics/metabolism, Clinical article, Fas ligand protein, Blotting, Western, CRF Receptor, Type 1, Receptors, Corticotropin-Releasing Hormone, Article, Ovarian cancer, Cell Line, Tumor, Cancer cell culture, Humans, RNA, Messenger, Human tissue, Immune response, Lymphocyte activation, Cell Proliferation, Neoplasm Staging, Neoplastic, Human cell, Neoplasm staging, Protein expression, Rna, Fas Ligand Protein/genetics/immunology/*metabolism, Cell line, Translational Therapeutics, Controlled study, Corticotropin releasing factor receptor 2, Corticotropin releasing factor receptor 1
Corticotropin-Releasing Hormone, Messenger rna, Messenger, Apoptosis, Cancer staging, Ovarian neoplasms, Fas ligand, Cancer growth, Corticotropin-Releasing Hormone/genetics/*metabolism/physiology, Receptors, Immune privilege, Regulatory mechanism, Up-regulation, Lymphocytes, Fluorescent Antibody Technique, Indirect, Reverse transcriptase polymerase chain reaction, Cell proliferation, Priority journal, Gene expression regulation, Corticotropin releasing factor, Ovarian Neoplasms, Tumor, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Caspases/metabolism, Receptors, Corticotropin-Releasing Hormone/genetics/metabolism, Correlation analysis, Lymphocytes/cytology/immunology/metabolism, Immunohistochemistry, Up-Regulation, Gene Expression Regulation, Neoplastic, Peripheral lymphocyte, Fluorescent antibody technique, Crh, Caspases, Ovarian Neoplasms/genetics/metabolism/*pathology, Female, Western, Apoptosis/immunology, Human, Corticotropin-releasing hormone, Indirect, Fas Ligand Protein, Ovary cancer, RNA, Messenger/genetics/metabolism, Clinical article, Fas ligand protein, Blotting, Western, CRF Receptor, Type 1, Receptors, Corticotropin-Releasing Hormone, Article, Ovarian cancer, Cell Line, Tumor, Cancer cell culture, Humans, RNA, Messenger, Human tissue, Immune response, Lymphocyte activation, Cell Proliferation, Neoplasm Staging, Neoplastic, Human cell, Neoplasm staging, Protein expression, Rna, Fas Ligand Protein/genetics/immunology/*metabolism, Cell line, Translational Therapeutics, Controlled study, Corticotropin releasing factor receptor 2, Corticotropin releasing factor receptor 1
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