SEMA3C induces androgen synthesis in prostatic stromal cells through paracrine signaling.
Prostate
; 81(6): 309-317, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33503318
ABSTRACT
BACKGROUND:
Castration resistant prostate cancer progression is associated with an acquired intratumoral androgen synthesis. Signaling pathways that can upregulate androgen production in prostate tumor microenvironment are not entirely known. In this study, we investigate the potential effect of a secreted signaling protein named semaphorin 3C (SEMA3C) on steroidogenic activities of prostatic stromal cells.METHODS:
We treated human primary prostate stromal cells (PrSC) with 1uM recombinant SEMA3C protein and androgen precursor named dehydroepiandrosterone (DHEA) 1.7uM. Also, to test SEMA3C's effect on the conversion of DHEA to androgens, we exposed PrSCs to the conditioned media derived from LNCaP cells that were transduced with a lentiviral vector harboring full length SEMA3C gene or empty vector (CM-LNSEMA3C or CM-LNVector ). Then, liquid chromatography-mass spectrometry was performed on steroids isolated from PrSCs media. The messnger RNA expression of steroidogenic enzymes in PrSCs was quantified by quantitative polymerase chain reaction.RESULTS:
Recombinant SEMA3C had no effect on steroidogenic activities in PrSCs. However, key steroidogenic enzymes expression and androgen synthesis were upregulated in PrSCs treated with CM-LNSEMA3C , compared to those treated with CM-LNVector . These results suggest that steroidogenic activities in PrSCs were upregulated in response to a signaling factor in CM-LNSEMA3C , other than SEMA3C. We hypothesized that SEMA3C overexpression in LNCaP cells affected androgen synthesis in PrSCs through sonic hedgehog (Shh) pathway activation in PrSCs. We verified this effect by blocking Shh signaling with smoothened antagonist.CONCLUSION:
Based on known ability of Shh signaling pathway to activate steroidogenesis in stromal cells, we suggest that SEMA3C overexpression in LNCaP cells can upregulate Shh which in turn is able to stimulate steroidogenic activities in prostatic stromal cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Próstata
/
Células Estromais
/
Semaforinas
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Proteínas Hedgehog
/
Androgênios
Limite:
Humans
/
Male
Idioma:
En
Revista:
Prostate
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá