Granulocyte colony-stimulating factor receptor signalling via Janus kinase 2/signal transducer and activator of transcription 3 in ovarian cancer.
BACKGROUND
Ovarian cancer remains a major cause of cancer mortality in women, with only limited understanding of disease aetiology at the molecular level. Granulocyte colony-stimulating factor (G-CSF) is a key regulator of both normal and emergency haematopoiesis, and is used clinically to aid haematopoietic recovery following ablative therapies for a variety of solid tumours including ovarian cancer.


METHODS
The expression of G-CSF and its receptor, G-CSFR, was examined in primary ovarian cancer samples and a panel of ovarian cancer cell lines, and the effects of G-CSF treatment on proliferation, migration and survival were determined.


RESULTS
G-CSFR was predominantly expressed in high-grade serous ovarian epithelial tumour samples and a subset of ovarian cancer cell lines. Stimulation of G-CSFR-expressing ovarian epithelial cancer cells with G-CSF led to increased migration and survival, including against chemotherapy-induced apoptosis. The effects of G-CSF were mediated by signalling via the downstream JAK2/STAT3 pathway.


CONCLUSIONS
This study suggests that G-CSF has the potential to impact on ovarian cancer pathogenesis, and that G-CSFR expression status should be considered in determining appropriate therapy.
1] School of Medicine, Deakin University, Geelong, Victoria 3216, Australia [2] Strategic Research Centre in Molecular and Medical Research, Deakin University, Geelong, Victoria 3216, Australia.
J
J
Kumar
1] School of Medicine, Deakin University, Geelong, Victoria 3216, Australia [2] Strategic Research Centre in Molecular and Medical Research, Deakin University, Geelong, Victoria 3216, Australia.
F W
FW
Fraser
Women's Cancer Research Centre, Royal Women's Hospital, Parkville, Victoria 3052, Australia.
C
C
Riley
1] Women's Cancer Research Centre, Royal Women's Hospital, Parkville, Victoria 3052, Australia [2] Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria 3052, Australia.
N
N
Ahmed
1] School of Medicine, Deakin University, Geelong, Victoria 3216, Australia [2] Strategic Research Centre in Molecular and Medical Research, Deakin University, Geelong, Victoria 3216, Australia.
D R
DR
McCulloch
1] School of Medicine, Deakin University, Geelong, Victoria 3216, Australia [2] Strategic Research Centre in Molecular and Medical Research, Deakin University, Geelong, Victoria 3216, Australia.
A C
AC
Ward
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D000077216:Carcinoma, Ovarian Epithelial; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D053614:Janus Kinase 2 / Q000378:metabolism*; D060787:Neoplasm Grading; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D015850:Interleukin-6; D016184:Receptors, Colony-Stimulating Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016179:Granulocyte Colony-Stimulating Factor; D053614:Janus Kinase 2; D017239:Paclitaxel; D002945:Cisplatin