Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/130092
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Type: Journal article
Title: Reduced gonadotrophin receptor expression is associated with a more aggressive ovarian cancer phenotype
Author: Cheung, J.
Lokman, N.A.
Abraham, R.D.
Macpherson, A.M.
Lee, E.
Grutzner, F.
Ghinea, N.
Oehler, M.K.
Ricciardelli, C.
Citation: International Journal of Molecular Sciences, 2021; 22(1):71-1-71-21
Publisher: MDPI AG
Issue Date: 2021
ISSN: 1422-0067
1422-0067
Statement of
Responsibility: 
Janelle Cheung, Noor A. Lokman, Riya D. Abraham, Anne M. Macpherson, Eunice Lee , Frank Grutzner, Nicolae Ghinea, Martin K. Oehler and Carmela Ricciardelli
Abstract: Follicle-stimulating hormone (FSH) and luteinising hormone (LH) play important roles in regulating cell growth and proliferation in the ovary. However, few studies have explored the expression of FSH and LH receptors (FSHR and LHCGR) in ovarian cancer, and their functional roles in cancer progression remain inconclusive. This study investigated the potential impact of both mRNA (FSHR, LHCGR) and protein (FSHR, LHCGR) expression on ovarian cancer progression using publicly available online databases, qRT-PCR (high grade serous ovarian cancers, HGSOC, n = 29 and benign ovarian tumors, n = 17) and immunohistochemistry (HGSOC, n = 144). In addition, we investigated the effect of FSHR and LHCGR siRNA knockdown on the pro-metastatic behavior of serous ovarian cancer cells in vitro. High FSHR or high LHCGR expression in patients with all subtypes of high-grade ovarian cancer was significantly associated with longer progression-free survival (PFS) and overall survival (OS). High FSHR protein expression was associated with increased PFS (p = 0.050) and OS (p = 0.025). HGSOC patients with both high FSHR and high LHCGR protein levels had the best survival outcome, whilst both low FSHR and low LHCGR expression was associated with poorest survival (p = 0.019). Knockdown of FSHR significantly increased the invasion of serous ovarian cancer cells (OVCAR3 and COV362) in vitro. LHCGR knockdown also promoted invasion of COV362 cells. This study highlights that lower FSHR and LHCGR expression is associated with a more aggressive epithelial ovarian cancer phenotype and promotes pro-metastatic behaviour.
Keywords: Ovarian cancer; serous ovarian cancer; gonadotropins; FSHR; LHCGR; cancer progression
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
DOI: 10.3390/ijms22010071
Grant ID: ARC
Published version: http://dx.doi.org/10.3390/ijms22010071
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