Dataset Information

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis.

ABSTRACT: 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.

SUBMITTER: Lorenzen M

PROVIDER: S-EPMC7352821 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis.

Lorenzen Mette M Nielsen John Erik JE Andreassen Christine Hjorth CH Juul Anders A Toft Birgitte Grønkær BG Rajpert-De Meyts Ewa E Daugaard Gedske G Blomberg Jensen Martin M

Cancers 20200526 6

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 ...[more]

PMID: 32466562

Similar Datasets

Project description:Background: Testicular germ cell tumor (TGCT) incidence has increased over the last 40 years in the United States. In contrast to TGCT among infants, it is hypothesized that TGCT in adolescents and young men is the result of sex steroid hormone imbalance during early fetal development. However, little is known about the neonatal period when abrupt hormonal changes occur, and direct supporting evidence is scarce due to the difficulties in obtaining prediagnostic specimens.Methods: We conducted a population-based case-control study examining hormone levels at birth among 91 infants (0-4 years) and 276 adolescents (15-19 years) diagnosed with TGCT, and 344 matched controls. Estrogen and androgen levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from archived newborn dried blood spots. Logistic regression models were used to estimate the association between each hormone level and TGCT risk.Results: Higher levels of androstenedione were associated with increased TGCT risk among adolescents [odds ratio (OR): 2.33, 95% confidence interval (CI): 1.37-3.97 for highest vs. lowest quartile; P trend = 0.003] but not among infants (OR: 0.70, 95% CI: 0.28-1.77). A similar pattern was observed for testosterone (OR: 1.73, 95% CI: 1.00-3.00,) although the trend was not significant (P trend = 0.12). Associations were stronger among non-Hispanic white subjects, relative to Hispanics. There was no difference by tumor histologic subtype. Estriol (the only detectable estrogen) was not associated with TGCT risk in either age group.Conclusions: Higher levels of neonatal androgens were associated with increased risk of TGCT among adolescents, suggesting that early life hormone levels are related to the later development of TGCT.Impact: This is the first study with direct measures of sex steroid hormones to examine the relationship between estrogens and androgens at birth and risk of adolescent TGCT. Cancer Epidemiol Biomarkers Prev; 27(4); 488-95. ©2018 AACR.

Project description:Testicular Germ Cell Tumors (TGCTs) are a rare group of neoplasms and the most common solid malignancy arising in young male adults. Despite the good response of these tumors to platinum-based chemotherapy, some patients are refractory to treatment and present poor clinical outcomes. During carcinogenesis and tumor development, cancer cells reprogram energy metabolism toward a hyper-glycolytic phenotype, an emerging hallmark of cancer. This phenomenon, known as the Warburg effect or aerobic glycolysis, involves overexpression of metabolism-related proteins, like glucose and monocarboxylate transporters, pH regulators and intracellular glycolytic enzymes. The metabolic profile of TGCTs is very little explored and, recently, this metabolic rewiring of cancer cells has been associated with aggressive clinicopathological characteristics of these tumors. The overexpression of monocarboxylate transporter 4 (MCT4) in TGCTs has been pointed out as a poor prognostic factor, as well as a promising therapeutic target. As a result, the main aim of the present study was to evaluate the prognostic value of key metabolism-related proteins in TGCTs. The immunohistochemical expressions of CD44 (as a monocarboxylate transporter chaperone), glucose transporter 1 (GLUT1), carbonic anhydrase IX (CAIX), hexokinase II (HKII) and lactate dehydrogenase V (LDHV) were evaluated in a series of 148 adult male patients with TGCTs and associated with clinicopathological parameters. In addition, paired normal tissues were also evaluated. The sample included 75 seminoma and 73 non-seminoma tumors. GLUT1 and CD44 expression was significantly increased in malignant samples when compared to paired normal samples. Conversely, HKII and LDHV expressions were significantly decreased in malignant samples. Concerning the clinicopathological values, CAIX expression was significantly associated with disease recurrence, while HKII expression was significantly associated with aggressive characteristics of TGCTs, including higher staging and non-seminoma histology. In conclusion, this study brings new insights on the metabolic characteristics of TGCTs, showing alterations in the expression of proteins related with the Warburg effect, as well as associations of the hyper-glycolytic and acid-resistant phenotype with aggressive clinicopathological parameters.

Dataset Information

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis.

Publications

Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets