1. Academic Validation
  2. Peri-Prostatic Adipocyte-Released TGFβ Enhances Prostate Cancer Cell Motility by Upregulation of Connective Tissue Growth Factor

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

  • Biomedicines. 2021 Nov 15;9(11):1692. doi: 10.3390/biomedicines9111692.
Evelina La Civita 1 Antonietta Liotti 1 Michele Cennamo 1 Felice Crocetto 2 Matteo Ferro 3 Pasquale Liguoro 1 Amelia Cimmino 4 Ciro Imbimbo 2 Francesco Beguinot 1 Pietro Formisano 1 Daniela Terracciano 1
Affiliations

Affiliations

  • 1 Department of Translational Medical Sciences, University of Naples "Federico II", 80131 Naples, Italy.
  • 2 Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University of Naples "Federico II", 80131 Naples, Italy.
  • 3 Division of Urology, European Institute of Oncology, 20141 Milan, Italy.
  • 4 Institute of Genetics and Biophysic, National Research Council, 80131 Naples, Italy.
Abstract

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.

Keywords

TGFβ1; adipocytes; cell migration; peri-prostatic adipose tissue; prostate cancer.

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