Faculté de Médecine, Inserm UMR1069 "Nutrition, Croissance et Cancer" Université François Rabelais, Tours, France.
Department of Medical Oncology, CHU Tours, Tours, France.
Prostate. 2024 Mar;84(4):358-367. doi: 10.1002/pros.24655. Epub 2023 Dec 19.
Periprostatic 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.
The 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.
Although 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.
These 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.
前列腺周围脂肪组织（PPAT）可能调节前列腺癌（PCa）的进展。我们根据其脂肪酸（FA）组成和肿瘤特征分析了 PPAT 对癌细胞的影响变化。
通过免疫组织化学分析了包含 59 例 pT3 PCa 的组织微阵列中的侵袭性标志物 Ki67 和 Zeb1 以及在 PCa 进展过程中可能被修饰的表观遗传标记，这些 PCa 包括与属于同一肿瘤的 PPAT 接触的前列腺内区域和前列腺外焦点。此外，我们还将 PC3 和 LNCaP 细胞系与 PPAT 共培养，然后分析其 FA 组成。
尽管 PPAT 与癌细胞的接触总体上导致 Ki67 和 Zeb1 的增加以及表观遗传标记 5MC、5HMC 和 H3K27ac 的减少，但这些影响具有高度异质性。前列腺外区域的增殖增加与国际泌尿病理学会评分相关。PC3 和 LNCaP 与 PPAT 的共培养导致 Ki67、Zeb1 和 H3K27me3 的增加，但仅在与侵袭性 PCa 相关的 PPAT 中观察到。PC3 的增殖与 PPAT 中高 20.2n-6 和低 20.5n-3 相关。
这些结果表明，PPAT 对癌细胞的影响可能取决于 PCa 特征和 PPAT 组成，并可能导致提出营养补充建议。
