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Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform

Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated ad...

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Autores principales: Liotti, Antonietta, La Civita, Evelina, Cennamo, Michele, Crocetto, Felice, Ferro, Matteo, Guadagno, Elia, Insabato, Luigi, Imbimbo, Ciro, Palmieri, Alessandro, Mirone, Vincenzo, Liguoro, Pasquale, Formisano, Pietro, Beguinot, Francesco, Terracciano, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251776/
https://www.ncbi.nlm.nih.gov/pubmed/33734457
http://dx.doi.org/10.1002/pros.24117
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author Liotti, Antonietta
La Civita, Evelina
Cennamo, Michele
Crocetto, Felice
Ferro, Matteo
Guadagno, Elia
Insabato, Luigi
Imbimbo, Ciro
Palmieri, Alessandro
Mirone, Vincenzo
Liguoro, Pasquale
Formisano, Pietro
Beguinot, Francesco
Terracciano, Daniela
author_facet Liotti, Antonietta
La Civita, Evelina
Cennamo, Michele
Crocetto, Felice
Ferro, Matteo
Guadagno, Elia
Insabato, Luigi
Imbimbo, Ciro
Palmieri, Alessandro
Mirone, Vincenzo
Liguoro, Pasquale
Formisano, Pietro
Beguinot, Francesco
Terracciano, Daniela
author_sort Liotti, Antonietta
collection PubMed
description Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL‐xL, BCL‐2, and TUBB2B. AG1024, a well‐known IGF‐1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF‐1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte‐released factors and IGF‐1 axis to overcome DCTX resistance in patients with PCa.
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spelling pubmed-82517762021-07-07 Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform Liotti, Antonietta La Civita, Evelina Cennamo, Michele Crocetto, Felice Ferro, Matteo Guadagno, Elia Insabato, Luigi Imbimbo, Ciro Palmieri, Alessandro Mirone, Vincenzo Liguoro, Pasquale Formisano, Pietro Beguinot, Francesco Terracciano, Daniela Prostate Original Articles Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL‐xL, BCL‐2, and TUBB2B. AG1024, a well‐known IGF‐1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF‐1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte‐released factors and IGF‐1 axis to overcome DCTX resistance in patients with PCa. John Wiley and Sons Inc. 2021-03-18 2021-05-15 /pmc/articles/PMC8251776/ /pubmed/33734457 http://dx.doi.org/10.1002/pros.24117 Text en © 2021 The Authors. The Prostate published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Liotti, Antonietta
La Civita, Evelina
Cennamo, Michele
Crocetto, Felice
Ferro, Matteo
Guadagno, Elia
Insabato, Luigi
Imbimbo, Ciro
Palmieri, Alessandro
Mirone, Vincenzo
Liguoro, Pasquale
Formisano, Pietro
Beguinot, Francesco
Terracciano, Daniela
Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform
title Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform
title_full Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform
title_fullStr Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform
title_full_unstemmed Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform
title_short Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF‐1 upregulation of TUBB2B beta‐tubulin isoform
title_sort periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine igf‐1 upregulation of tubb2b beta‐tubulin isoform
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251776/
https://www.ncbi.nlm.nih.gov/pubmed/33734457
http://dx.doi.org/10.1002/pros.24117
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