Expression of ERα, its ERαΔ3 Splice Variant and γ-SYNUCLEIN in Ovarian Cancer: A Pilot Study
Karen T. Cheung
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK and Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston PR2 9RR, UK.
Siân E. Taylor
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK and Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston PR2 9RR, UK.
Imran I. Patel
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK.
Adam J. Bentley
Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
Helen F. Stringfellow
Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston PR2 9RR, UK.
Nigel J. Fullwood
Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
Pierre L. Martin-Hirsch
Lancashire Teaching Hospitals NHS Trust, Fulwood, Preston PR2 9RR, UK.
Francis L. Martin *
Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, UK.
*Author to whom correspondence should be addressed.
Abstract
Aims: Ovarian cancer has the highest mortality of any gynaecological malignancy; this is due to rapid peritoneal spread of tumour cells and neovascularization. Understanding the mechanisms underlying this is critical to developing early diagnostic or treatment strategies. We devised a pilot study to examine the role of γ-SYNUCLEIN (γ-SYN), oestrogen receptor (ER)α, and the splice variant ERαΔ3.
Methodology: With ethical approval, ovarian tissue was collected from patients (n=24) undergoing oopherectomy for non-ovarian pathology or primary surgery for suspected ovarian cancer. Quantitative gene expression analysis was employed for γ-SYN, ERα, and ERαΔ3. To identify the in situ localization, immunofluorescence for γ-syn was carried out.
Results: Ovarian tumour tissue exhibited an elevated expression of γ-SYN and high-grade tumours had an elevated ERαΔ3:ERα ratio compared with benign tissue. The majority of previous studies point to the γ-syn protein being present in epithelial cells of high-grade disease. Our study supports this, but additionally we conclusively identify its presence in the endothelial cells of vasculature surrounding low-grade disease; immunofluorescence was strongest in the apical cells surrounding the lumen.
Conclusion: Our results demonstrate for the first time that there are readily-expressed levels of γ-SYN and ERαΔ3 in normal ovarian tissue and ovarian tumours. In high-grade disease, γ-syn and an elevated ERαΔ3:ERα ratio might confer metastatic potential to the tumourigenic cells and promote neoangiogenesis. Future in vitro studies might be necessary to delineate such a mechanism, which could potentially be the basis of early intervention.
Keywords: Endothelial cells, ovarian cancer, ERα, ERαΔ3, γ-SYNUCLEIN, neoangiogenesis