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.
- 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.
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.