Biomedicines (Nov 2021)

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

  • Evelina La Civita,
  • Antonietta Liotti,
  • Michele Cennamo,
  • Felice Crocetto,
  • Matteo Ferro,
  • Pasquale Liguoro,
  • Amelia Cimmino,
  • Ciro Imbimbo,
  • Francesco Beguinot,
  • Pietro Formisano,
  • Daniela Terracciano

DOI
https://doi.org/10.3390/biomedicines9111692
Journal volume & issue
Vol. 9, no. 11
p. 1692

Abstract

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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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