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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: La Civita, Evelina, Liotti, Antonietta, Cennamo, Michele, Crocetto, Felice, Ferro, Matteo, Liguoro, Pasquale, Cimmino, Amelia, Imbimbo, Ciro, Beguinot, Francesco, Formisano, Pietro, Terracciano, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615771/
https://www.ncbi.nlm.nih.gov/pubmed/34829922
http://dx.doi.org/10.3390/biomedicines9111692
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author La Civita, Evelina
Liotti, Antonietta
Cennamo, Michele
Crocetto, Felice
Ferro, Matteo
Liguoro, Pasquale
Cimmino, Amelia
Imbimbo, Ciro
Beguinot, Francesco
Formisano, Pietro
Terracciano, Daniela
author_facet La Civita, Evelina
Liotti, Antonietta
Cennamo, Michele
Crocetto, Felice
Ferro, Matteo
Liguoro, Pasquale
Cimmino, Amelia
Imbimbo, Ciro
Beguinot, Francesco
Formisano, Pietro
Terracciano, Daniela
author_sort La Civita, Evelina
collection PubMed
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.
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spelling pubmed-86157712021-11-26 Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor La Civita, Evelina Liotti, Antonietta Cennamo, Michele Crocetto, Felice Ferro, Matteo Liguoro, Pasquale Cimmino, Amelia Imbimbo, Ciro Beguinot, Francesco Formisano, Pietro Terracciano, Daniela Biomedicines Article 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. MDPI 2021-11-15 /pmc/articles/PMC8615771/ /pubmed/34829922 http://dx.doi.org/10.3390/biomedicines9111692 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
La Civita, Evelina
Liotti, Antonietta
Cennamo, Michele
Crocetto, Felice
Ferro, Matteo
Liguoro, Pasquale
Cimmino, Amelia
Imbimbo, Ciro
Beguinot, Francesco
Formisano, Pietro
Terracciano, Daniela
Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615771/
https://www.ncbi.nlm.nih.gov/pubmed/34829922
http://dx.doi.org/10.3390/biomedicines9111692
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