Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor

Periprostatic adipose tissue (PPAT) has emerged as a key player in the prostate cancer (PCa) microenvironment. In this study, we evaluated the ability of PPAT to promote PCa cell migration, as well as the molecular mechanisms involved. Methods: We collected conditioned mediums from in vitro differen...

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Autores principales: Evelina La Civita, Antonietta Liotti, Michele Cennamo, Felice Crocetto, Matteo Ferro, Pasquale Liguoro, Amelia Cimmino, Ciro Imbimbo, Francesco Beguinot, Pietro Formisano, Daniela Terracciano
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/a4a980bb92f74dc9babe0bac00f3cabd
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spelling oai:doaj.org-article:a4a980bb92f74dc9babe0bac00f3cabd2021-11-25T16:50:54ZPeri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor10.3390/biomedicines91116922227-9059https://doaj.org/article/a4a980bb92f74dc9babe0bac00f3cabd2021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1692https://doaj.org/toc/2227-9059Periprostatic adipose tissue (PPAT) has emerged as a key player in the prostate cancer (PCa) microenvironment. In this study, we evaluated the ability of PPAT to promote PCa cell migration, as well as the molecular mechanisms involved. Methods: We collected conditioned mediums from in vitro differentiated adipocytes isolated from PPAT taken from PCa patients during radical prostatectomy. Migration was studied by scratch assay. Results: Culture with CM of human PPAT (AdipoCM) promotes migration in two different human androgen-independent (AI) PCa cell lines (DU145 and PC3) and upregulated the expression of CTGF. SB431542, a well-known TGFβ receptor inhibitor, counteracts the increased migration observed in presence of AdipoCM and decreased CTGF expression, suggesting that a paracrine secretion of TGFβ by PPAT affects motility of PCa cells. Conclusions: Collectively, our study showed that factors secreted by PPAT enhanced migration through CTGF upregulation in AI PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and TGFβ/CTGF axis to fight advanced PCa dissemination.Evelina La CivitaAntonietta LiottiMichele CennamoFelice CrocettoMatteo FerroPasquale LiguoroAmelia CimminoCiro ImbimboFrancesco BeguinotPietro FormisanoDaniela TerraccianoMDPI AGarticleadipocytesprostate cancerTGFβ1peri-prostatic adipose tissuecell migrationBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1692, p 1692 (2021)
institution DOAJ
collection DOAJ
language EN
topic adipocytes
prostate cancer
TGFβ1
peri-prostatic adipose tissue
cell migration
Biology (General)
QH301-705.5
spellingShingle adipocytes
prostate cancer
TGFβ1
peri-prostatic adipose tissue
cell migration
Biology (General)
QH301-705.5
Evelina La Civita
Antonietta Liotti
Michele Cennamo
Felice Crocetto
Matteo Ferro
Pasquale Liguoro
Amelia Cimmino
Ciro Imbimbo
Francesco Beguinot
Pietro Formisano
Daniela Terracciano
Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
description Periprostatic adipose tissue (PPAT) has emerged as a key player in the prostate cancer (PCa) microenvironment. In this study, we evaluated the ability of PPAT to promote PCa cell migration, as well as the molecular mechanisms involved. Methods: We collected conditioned mediums from in vitro differentiated adipocytes isolated from PPAT taken from PCa patients during radical prostatectomy. Migration was studied by scratch assay. Results: Culture with CM of human PPAT (AdipoCM) promotes migration in two different human androgen-independent (AI) PCa cell lines (DU145 and PC3) and upregulated the expression of CTGF. SB431542, a well-known TGFβ receptor inhibitor, counteracts the increased migration observed in presence of AdipoCM and decreased CTGF expression, suggesting that a paracrine secretion of TGFβ by PPAT affects motility of PCa cells. Conclusions: Collectively, our study showed that factors secreted by PPAT enhanced migration through CTGF upregulation in AI PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and TGFβ/CTGF axis to fight advanced PCa dissemination.
format article
author Evelina La Civita
Antonietta Liotti
Michele Cennamo
Felice Crocetto
Matteo Ferro
Pasquale Liguoro
Amelia Cimmino
Ciro Imbimbo
Francesco Beguinot
Pietro Formisano
Daniela Terracciano
author_facet Evelina La Civita
Antonietta Liotti
Michele Cennamo
Felice Crocetto
Matteo Ferro
Pasquale Liguoro
Amelia Cimmino
Ciro Imbimbo
Francesco Beguinot
Pietro Formisano
Daniela Terracciano
author_sort Evelina La Civita
title Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
title_short Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
title_full Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
title_fullStr Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
title_full_unstemmed Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
title_sort peri-prostatic adipocyte-released tgfβ enhances prostate cancer cell motility by upregulation of connective tissue growth factor
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/a4a980bb92f74dc9babe0bac00f3cabd
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