Periprostatic Adipose Tissue Displays a Chronic Hypoxic State that Limits Its Expandability

Roumiguié, M.; Estève, David; Manceau, Cécile; Toulet, Aurélie; Gilleron, Jérôme; Belles, Chloé; Jia, Yiyue; Houël, Cynthia; Péricart, Sarah; Gonidec, Sophie Le; Valet, Philippe; Cormont, Mireille; Tanti, Jean‐François; Malavaud, Bernard; Bouloumié, Anne; Milhas, Delphine; Müller, Cathérine

doi:10.1016/j.ajpath.2022.03.008

Cited by 11 publications

(22 citation statements)

References 60 publications

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“…In the cohort of PCa patients, PPAT volume was independent of BMI (Fig. 1C), as we reported previously for a smaller cohort (Roumiguié et al, 2022); this was true also for the patients without PCa (Fig. 1C).…”

Section: Resultssupporting

confidence: 87%

“…As shown before (Roumiguié et al, 2022), PPAT exhibit a peculiar vascularization leading to chronic hypoxia and fibrosis that limits its expansion in obese individuals. To expand, collagen degradation occurs in high PPAT that exhibit hypertrophic adipocytes due to the increased expression of lipid transporters and the decreased expression of proteins involved in lipolysis, favoring lipid uptake over degradation.…”

Section: Discussionsupporting

confidence: 56%

“…The increased risk of advanced disease and PCa-specific mortality ranges from 6-12 % with every 5 kg/m 2 increase in body mass index (BMI) (Cao and Ma, 2011; Harrison et al, 2020). Although changes in PPAT function occur in obesity (Estève et al, 2020), many studies have shown that, unlike all other WAT, the volume of PPAT, as measured by multiparametric magnetic resonance imaging (mpMRI), does not correlate with BMI (Woo et al, 2015; Roumiguié et al, 2022; Zhang et al, 2014). This failure of PPAT to expand in obese individuals may be explained by the chronic hypoxic state of PPAT, which induces fibrosis (Roumiguié et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Although the volume of PPAT in an individual does not correlate with his BMI, it does vary considerably between individuals (Zhang et al, 2014; Woo et al, 2015; Roumiguié et al, 2022). Recent clinical studies have demonstrated that patients with large amounts of PPAT have more aggressive PCa than the patients with low amounts (Nassar et al, 2018), suggesting that the abundance of PPAT might be used to stratify patients’ risk.…”

Section: Introductionmentioning

confidence: 99%

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Collagen remodeling leads to inflammation-free expansion of periprostatic adipose tissue and promotes prostate cancer progression

Estève

Toulet

Roumiguié

et al. 2023

Preprint

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Periprostatic adipose tissue (PPAT) abundance correlates with prostate cancer progression, but the mechanism remains unexplained. Here, we used a statistical approach to define abundant PPAT by normalizing PPAT volume to prostate volume in a cohort of 351 patients with a linear regression model. Applying this definition, we find tumors specifically from patients with abundant PPAT exhibit several hallmarks of aggressiveness, suggesting that PPAT abundance might be used to improve risk stratification. We show that abundant PPAT expands by adipocyte hypertrophy but this does not result in inflammation. Extensive extracellular matrix remodeling, notably of the collagen network, and decreased expression of mechano-sensing proteins in adipocytes explains this inflammation-free expansion by decreasing the mechanical constraints on the adipocytes. Moreover, collagen VI degradation in abundant PPAT is associated with production of endotrophin, a matrikine that promotes cancer progression. We find high levels of endotrophin specifically in the urine of patients with abundant PPAT, indicating the clinical relevance of our findings.

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Section: Resultssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Collagen remodeling leads to inflammation-free expansion of periprostatic adipose tissue and promotes prostate cancer progression

Estève

Toulet

Roumiguié

et al. 2023

Preprint

Self Cite

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“…It is becoming increasingly clear that PPAT is biologically distinct from other adipose tissues. Unlike other adipose depots, elevated levels of chronic inflammatory and fibrosis factors have been observed in PPAT, and its volume is independent of the state of obesity [ 33 , 34 ]. A range of mechanisms have been proposed to explain the effects of PPAT on PCa development, including the release of growth factors, stimulation of inflammatory signalling activators, hyperinsulinemia, altered adipokine profiles, and increased lipid availability [ 35–37 ].…”

Section: Discussionmentioning

confidence: 99%

MRI-measured adipose features as predictive factors for detection of prostate cancer in males undergoing systematic prostate biopsy: a retrospective study based on a Chinese population

et al. 2022

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In this study, we retrospectively evaluated the data of 901 men undergoing ultrasonography-guided systematic prostate biopsy between March 2013 and May 2022. Adipose features, including periprostatic adipose tissue (PPAT) thickness and subcutaneous fat thickness, were measured using MRI before biopsy. Prediction models of all PCa and clinically significant PCa (csPCa) (Gleason score higher than 6) were established based on variables selected by multivariate logistic regression and prediction nomograms were constructed. Patients with PCa had higher PPAT thickness (4.64 [3.65–5.86] vs. 3.54 [2.49–4.51] mm, p < 0.001) and subcutaneous fat thickness (29.19 [23.05–35.95] vs. 27.90 [21.43–33.93] mm, p = 0.013) than those without PCa. Patients with csPCa had higher PPAT thickness (4.78 [3.80–5.88] vs. 4.52 [3.80–5.63] mm, p = 0.041) than those with non-csPCa. Adding adipose features to the prediction models significantly increased the area under the receiver operating characteristics curve for the prediction of all PCa (0.850 vs . 0.819, p < 0.001) and csPCa (0.827 vs . 0.798, p < 0.001). Based on MRI-measured adipose features and clinical parameters, we established two nomograms that were simple to use and could improve patient selection for prostate biopsy in Chinese population.

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Variable effects of periprostatic adipose tissue on prostate cancer cells: Role of adipose tissue lipid composition and cancer cells related factors

Cancel,

Crottes,

Bellanger

et al. 2023

The Prostate

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BackgroundPeriprostatic adipose tissue (PPAT) is likely to modulate prostate cancer (PCa) progression. We analyzed the variations in the effect of PPAT on cancer cells, according to its fatty acid (FA) composition and tumor characteristics.MethodsThe expression of markers of aggressiveness Ki67 and Zeb1, and epigenetic marks that could be modified during PCa progression, was analyzed by immunohistochemistry on a tissue‐micro‐array containing 59 pT3 PCa, including intra‐prostatic areas and extra‐prostatic foci in contact with PPAT belonging to the same tumor. In addition, we cocultivated PC3 and LNCaP cell lines with PPAT, which were then analyzed for FA composition.ResultsAlthough the contact between PPAT and cancer cells led overall to an increase in Ki67 and Zeb1, and a decrease in the epigenetic marks 5MC, 5HMC, and H3K27ac, these effects were highly heterogeneous. Increased proliferation in extra‐prostatic areas was associated with the international society of uropathology score. PC3 and LNCaP cocultures with PPAT led to increased Ki67, Zeb1 and H3K27me3, but only for PPAT associated with aggressive PCa. PC3 proliferation was correlated with high 20.2 n‐6 and low 20.5n‐3 in PPAT.ConclusionsThese results suggest that the effects of PPAT on cancer cells may depend on both PCa characteristics and PPAT composition, and could lead to propose nutritional supplementation.

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Periprostatic Adipose Tissue Displays a Chronic Hypoxic State that Limits Its Expandability

Cited by 11 publications

References 60 publications

Collagen remodeling leads to inflammation-free expansion of periprostatic adipose tissue and promotes prostate cancer progression

Collagen remodeling leads to inflammation-free expansion of periprostatic adipose tissue and promotes prostate cancer progression

MRI-measured adipose features as predictive factors for detection of prostate cancer in males undergoing systematic prostate biopsy: a retrospective study based on a Chinese population

Variable effects of periprostatic adipose tissue on prostate cancer cells: Role of adipose tissue lipid composition and cancer cells related factors

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