Leptin Receptor as a Potential Target to Inhibit Human Testicular Seminoma Growth.
Am J Pathol
; 189(3): 687-698, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30610844
ABSTRACT
Although in past decades the adipokine leptin and its own receptor have been considered as significant cancer biomarkers, their potential involvement in human testicular seminoma growth and progression remains unexplored. Here, we showed that the expression of leptin and its receptor was significantly higher in human testicular seminoma compared with normal adult testis. Human seminoma cell line TCam-2 also expressed leptin along with the long and short isoforms of leptin receptor, and in response to leptin treatment showed enhanced activation of its downstream effectors. In line with these results, leptin stimulation significantly increased the proliferation and migration of TCam-2 cells. Treatment of TCam-2 cells with the peptide Leu-Asp-Phe-Ile (LDFI), a full leptin-receptor antagonist, completely reversed the leptin-mediated effects on cell growth and motility as well as reduced the expression of several leptin-induced target genes. More importantly, the in vivo xenograft experiments showed that LDFI treatment markedly decreased seminoma tumor growth. Interestingly, LDFI-treated tumors showed reduced levels of the proliferation marker Ki-67 as well as decreased expression of leptin-regulated genes. Taken together, these data identify, for the first time, leptin as a key factor able to affect testicular seminoma behavior, highlighting leptin receptor as a potential target for novel potential treatments in this type of cancer.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Neoplasias Testiculares
/
Seminoma
/
Leptina
/
Receptores de Leptina
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Am J Pathol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia