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.
Highlights
Human periprostatic adipose tissue (PPAT) samples were obtained from 14 men who had undergone radical prostatectomy at the Division of Urology of the University Federico II (Naples, Italy) from September 2020 to January 2021
PPAT samples were obtained from 14 men who underwent radical prostatectomy: 3 adenomas; 3 low-grade Prostate cancer (PCa) [Gs ≤ 7(3 + 4)]; and 7 high-grade PCa [Gs ≥ 7(4 + 3)]
To investigate whether PPAT Conditioned Medium of human PPAT (AdipoCM) can influence cell motility in Pca cells, a series of wound-healing scratch assays were conducted on three different cell lines (LnCaP, DU145 and PC3)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The prostate is encircled by periprostatic adipose tissue (PPAT). This fat layer is contiguous to the gland capsule [12], making it plausible that PPAT affects the prostate cancer malignant phenotype [13,14]. Ribeiro et al [14] showed that PPAT collected from obese patients was able to enhance migration of androgen-dependent (AD) and castration-resistant PCa cell lines. The molecular crosstalk between PPAT and PCa cells plays a crucial role in the prostate tumor microenvironment (TME) and might be the basis for more aggressive disease behavior.
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