Luteinizing hormone/choriogonadotropin receptor (LHCGR) regulates gonadal testosterone production and recent studies have suggested a growth-regulatory role in somatic cancers. Here, we established that LHCGR is expressed in a fraction of seminoma cells and germ cell neoplasia in situ (GCNIS), and the seminoma-derived cell line TCam2 released LHCGR into the medium. LH treatment induced proliferation of TCam2 cells in vitro, while hCG treatment induced a non-significant 51% increase in volume of tumors formed in a TCam2 xenograft model. A specific ELISA was used to detect a soluble LHCGR in serum. Serum concentrations of soluble LHCGR could not distinguish 4 patients with GCNIS and 216 patients with testicular germ cell tumors (TGCTs) from 297 infertile or 148 healthy young men. Instead, serum LHCGR levels were significantly higher in 112 patients with a seminoma > 5 cm or elevated serum lactate dehydrogenase (LDH) compared with men harboring smaller seminomas < 2 cm or normal LDH levels. Serum LHCGR levels in TGCT patients could not predict relapse irrespective whether determined pre- or post-orchiectomy. Combined, these novel findings suggest that LHCGR may be directly involved in the progression and growth of seminomas, and our retrospective pilot study suggests that serum LHCGR may have some prognostic value in men with seminoma.
Cancers. 2020 May 26*** epublish ***
Mette Lorenzen, John Erik Nielsen, Christine Hjorth Andreassen, Anders Juul, Birgitte Grønkær Toft, Ewa Rajpert-De Meyts, Gedske Daugaard, Martin Blomberg Jensen
Group of Skeletal, Mineral and Gonadal Endocrinology, Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark., Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark., Department of Pathology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark., Department of Oncology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.