Human Periprostatic Adipose Tissue: its Influence on Prostate Cancer Cells

Abstract

Background/Aims: Adipose microenvironment is involved in signaling pathways that influence prostate cancer (PCa) progression. However, the role of human periprostatic adipose tissue (PPAT) from patients with benign prostatic hyperplasia (BPH) has not been studied and compared to that of PPAT from PCa patients. The aim of this paper was to investigate the influence of factors derived from both PPATs on the behavior of androgen-dependent and castration resistant PCa cells. Methods: PPAT conditioned media (CM) were obtained from tissue samples from patients with clinically primary PCa (TPPAT) or BPH (BPPAT). Cell adhesion, proliferation, migration and metalloproteinase expression were evaluated following exposure of LNCaP (androgen dependent) and PC3 (androgen independent) prostate cancer cell lines to BPPAT or TPPAT CM. Results: Proliferation or motility of LNCaP or PC3 cells were not significantly affected by TPPAT or BPPAT CM. The number of LNCaP but not PC3 cells attached to components of TPPAT CM significantly decreased compared to cells attached to BPPAT CM. PPAT produced and released pro-MMP-9. Zymograms demonstrated that TPPAT CM induced a significant increase in pro-MMP-9 activity compared to BPPAT CM in LNCaP cells but not in PC3 cells. Conclusions: We conclude that TPPAT released factors, such as pro-MMP-9, could induce the invasive capacity of LNCaP cells and speculate that PPAT derived factors could, in the early stages of prostate cancer, modulate disease progression.

Androgen control of lipid metabolism in prostate cancer: novel insights and future applications

“…While most research attention has focused on the actions of androgens on de novo lipogenesis, AR signaling may also regulate cellular uptake of exogenous lipids by prostate cancer cells (Pinthus et al 2007, Liu et al 2010, Mitra et al 2012, Sacca et al 2012, Taylor et al 2015. These lipids can be derived from dietary lipoproteins in the circulation, which are hydrolyzed by lipoprotein lipase to free fatty acids, or be released by lipolysis from stores in local adipose tissue depots that comprises a major component of the tumor microenvironment (Ribeiro et al 2012).…”

“…While there is conflicting data on the effect of obesity on the risk of developing prostate cancer, there is now strong evidence that obese men have more aggressive disease at diagnosis and a higher rate of recurrence following surgery (reviewed in Balaban et al (2015), Taylor et al (2015)). In cell line models, lipids taken up by prostate cancer cells can drive proliferation (Nieman et al 2013) and potentially invasiveness (Sacca et al 2012). Moreover, a recent report has demonstrated enhanced migration of prostate cancer cells induced by coculture with periprostatic-derived adipocytes from obese compared with lean mice (Laurent et al 2016).…”

Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

“…In addition, these models do not faithfully mimic the structure/function relationship of the human prostate, which is covered anteriorly by a prominent peri-prostatic adipose tissue (PPAT). PPAT mass is increased in obese humans and is a risk factor for high-grade disease [16, 17], and the secreted factors from human PPAT are reported to promote tumorigenicity in cultured cells [18, 19]. Hence, PPAT is likely to be functionally relevant for prostate cancer progression.…”

Dietary restriction: could it be considered as speed bump on tumor progression road?

“…Adipocytes localized near the tumor mass are called Bcancer-associated adipocytes^and show a reduction of adipose markers, such as HSL, APN, and resistin, and an increased expression of inflammatory cytokines (e.g., IL-6 and IL-1β) [61]. Adipocytes play an important role in cancer progression and may contribute to carcinogenesis and tumor invasiveness, since they are a source of pro-inflammatory cytokines, such as IL-6 and TNF-α, ROS, and matrix metalloproteases [62][63][64][65]. Moreover, adipocytes are able to secrete adipokines that increase angiogenesis, fibrosis, and inflammation by recruiting macrophages and endothelial cells inside the cancer microenvironment in a way mediated by NF-KB [66].…”