Novel functions of the luteinizing hormone/chorionic gonadotropin receptor in prostate cancer cells and patients
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Novel functions of the luteinizing hormone/chorionic gonadotropin receptor in prostate cancer cells and patients. / Stroomberg, Hein Vincent; Jørgensen, Anne; Brasso, Klaus; Nielsen, John Erik; Juul, Anders; Frederiksen, Hanne; Blomberg Jensen, Martin; Røder, Martin Andreas.
I: PLoS ONE, Bind 15, Nr. 9, e0238814, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Novel functions of the luteinizing hormone/chorionic gonadotropin receptor in prostate cancer cells and patients
AU - Stroomberg, Hein Vincent
AU - Jørgensen, Anne
AU - Brasso, Klaus
AU - Nielsen, John Erik
AU - Juul, Anders
AU - Frederiksen, Hanne
AU - Blomberg Jensen, Martin
AU - Røder, Martin Andreas
PY - 2020
Y1 - 2020
N2 - Prostate cancer (PCa) cells become castrate-resistant after initial tumor regression following castration-based lowering of testosterone (T). De-novo intra-tumoral steroid synthesis is a suggested biological mechanism of castration resistant PCa, but the regulators are unknown. Testicular T production is controlled by the luteinizing hormone/choriogonadotropin receptor (LHCGR). To elucidate the influence of LHCGR on PCa development the presence and effects of LHCGR in PCa and whether LHCGR in serum holds prognostic information in PCa patients is investigated. LHCGR expression was investigated by RT-PCR, WB, IHC, qPCR in PCa cell lines and prostatic tissue. Steroid production was measured in media from cell lines with LC-MS/MS and expression of steroidogenic enzymes with qPCR. Serum LHCGR (sLHCGR) was measured with ELISA in PCa patients (N = 157). Presence of LHCGR was established in prostatic tissue and PCa cell lines. Cell proliferation increased by 1.29-fold in LNCaP (P = 0.007) and 1.33-fold in PC-3 cells (P = 0.0007), when stimulated by luteinizing hormone. Choriogonadotropin stimulation decreased proliferation 0.93-fold in DU145 cells (P = 0.05), but none of the treatments altered steroid metabolite secretion. Low sLHCGR concentration was associated with a higher risk of biochemical failure after radical prostatectomy (HR = 3.05, P = 0.06) and castration resistance (HR = 6.92, P = 0.004) compared to high sLHCGR concentration. LHCGR is expressed in PCa and may exert a growth regulatory role in PCa derived cell lines. A potential prognostic role of sLHCGR for determining recurrence risk in PCa patients is found in this pilot study but needs verification in larger cohorts.
AB - Prostate cancer (PCa) cells become castrate-resistant after initial tumor regression following castration-based lowering of testosterone (T). De-novo intra-tumoral steroid synthesis is a suggested biological mechanism of castration resistant PCa, but the regulators are unknown. Testicular T production is controlled by the luteinizing hormone/choriogonadotropin receptor (LHCGR). To elucidate the influence of LHCGR on PCa development the presence and effects of LHCGR in PCa and whether LHCGR in serum holds prognostic information in PCa patients is investigated. LHCGR expression was investigated by RT-PCR, WB, IHC, qPCR in PCa cell lines and prostatic tissue. Steroid production was measured in media from cell lines with LC-MS/MS and expression of steroidogenic enzymes with qPCR. Serum LHCGR (sLHCGR) was measured with ELISA in PCa patients (N = 157). Presence of LHCGR was established in prostatic tissue and PCa cell lines. Cell proliferation increased by 1.29-fold in LNCaP (P = 0.007) and 1.33-fold in PC-3 cells (P = 0.0007), when stimulated by luteinizing hormone. Choriogonadotropin stimulation decreased proliferation 0.93-fold in DU145 cells (P = 0.05), but none of the treatments altered steroid metabolite secretion. Low sLHCGR concentration was associated with a higher risk of biochemical failure after radical prostatectomy (HR = 3.05, P = 0.06) and castration resistance (HR = 6.92, P = 0.004) compared to high sLHCGR concentration. LHCGR is expressed in PCa and may exert a growth regulatory role in PCa derived cell lines. A potential prognostic role of sLHCGR for determining recurrence risk in PCa patients is found in this pilot study but needs verification in larger cohorts.
KW - Aged
KW - Chorionic Gonadotropin/pharmacology
KW - Humans
KW - Luteinization/drug effects
KW - Luteinizing Hormone/metabolism
KW - Male
KW - Middle Aged
KW - Pilot Projects
KW - Prostate/pathology
KW - Prostatectomy/adverse effects
KW - Prostatic Neoplasms/physiopathology
KW - Receptors, LH/metabolism
KW - Testis/metabolism
KW - Testosterone/metabolism
KW - Tumor Cells, Cultured
U2 - 10.1371/journal.pone.0238814
DO - 10.1371/journal.pone.0238814
M3 - Journal article
C2 - 32881970
VL - 15
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e0238814
ER -
ID: 256580305