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.
Laboratory of Human Reproduction, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.
V
V
Minas
A
A
Rolaki
S N
SN
Kalantaridou
J
J
Sidiropoulos
S
S
Mitrou
G
G
Petsas
U
U
Jeschke
E A
EA
Paraskevaidis
G
G
Fountzilas
G P
GP
Chrousos
N
N
Pavlidis
A
A
Makrigiannakis
D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D020169:Caspases