Reproductive Endocrinology
Jesús M. Pérez-Gómez 1,2,3,4 , Prudencio Sáez-Martínez 1,2,3,4 , Juan M. Jiménez-Vacas 1,2,3,4 , Vicente Herrero-Aguayo 1,2,3,4 , Sergio Pedraza-Arévalo 1,2,3,4 , Enrique Gómez-Gómez 1,2,3,4 , Antonio J. León-González 1,2,3,4 , Justo P. Castaño 1,2,3,4 , Antonio J. Martínez-Fuentes 1,2,3,4 , Manuel D. Gahete 1,2,3,4 & Raúl M. Luque 1,2,3,4
1[email protected]; 2Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; 3Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain; 3Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain; 4CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain; 5Urology Service, HURS/IMIBIC, 14004 Cordoba, Spain
Background: Somatostatin (SST)/Cortistatin (CORT) system is a complex hormonal axis involved in the progression of several tumor types. However, its role has not been explored in prostate cancer (PCa), one of the most common type among men.
Objectives: We aimed to investigate the presence and the pathophysiological role of SST/CORT in PCa.
Methods: We analysed functional parameters in response to SST and CORT and to CORT-silencing in the normal prostate cell-line RWPE-1 and in different PCa-derived human cell lines [androgen-dependent (AD): LNCaP, and androgen-independent (AI): 22Rv1 and PC-3], which are models of hormone-sensitive and Castration-Resistant PCa, respectively. Moreover, mechanistic approaches were performed in response to SST/CORT treatment and CORT-silencing to determine the main pathways related to SST/CORT-axis in PCa cells. Additionally, in silico analysis using external databases were performed.
Results: SST and CORT inhibited proliferation and migration capacity in AI-PCa cells, but not in AD-PCa or in normal cells. Mechanistically, the antitumor capacity of these peptides was associated to the modulation of important oncogenic signalling pathways (AKT/JNK). Among all SST-receptors, only SSTR5 was significantly overexpressed in AI-PCa cells compared to normal-cells, suggesting that the SST/CORT actions in PCa cells might be mainly exerted through SSTR5. Remarkably, CORT was highly expressed, while SST was not detected, in all prostate cell lines analysed, suggesting that CORT could be exerting antitumor actions in PCa cells through an autocrine/paracrine mechanism. In support of this, CORT-silencing drastically increased the proliferation rate of AI-PCa cells. Finally, CORT expression was correlated with key clinical parameters in two in silico cohorts.
Conclusions: Altogether, these results indicate that some elements of the SST/CORT system could be useful as a new therapeutic option in AI-PCa cells, an idea that deserve further investigation.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more