Obesity is an established risk factor for the development and progression of prostate cancer (PC). This study used adipose conditioned media (ACM) from differentiated adipocytes to assess its effect on PC development and aggressiveness. Due to limited research on ACM's impact on isolated PC stem cells (PCSCs), we also examined CD44+ PCSCs. ACM notably boosted interleukin‐1β (IL‐1β), IL‐6, and IL‐8 production in normal prostate epithelial cells and LNCaP cells. It also increased IL‐6 and IL‐8 production in PC3 and CD44+ LNCaP cells, and IL‐1β and IL‐6 production in CD44+ PC3 cells. This indicates that ACM induces the production of inflammatory cytokines in both cancer and prostate epithelial cells. Furthermore, ACM promoted proliferation in androgen receptor (AR)‐negative PC3 cells, CD44+ PC3 PCSCs, and nonmalignant RWPE cells, without affecting AR‐positive LNCaP cells. In addition, ACM‐enhanced invasion and migration potential in both PC3 and CD44+ PC3 cells. Western blot analysis indicated the involvement of NF‐κB and AKT pathways in ACM‐induced proliferation in PC3 cells and NF‐κB in PCSCs. In ACM‐treated PC3 cells, E‐cadherin was downregulated, while N‐cadherin, Snail, vimentin, fibronectin, and Twist were upregulated, suggesting ACM‐induced invasion via classical epithelial‐to‐mesenchymal transition (EMT) pathways. In response to ACM, PCSCs exhibited increased expression of E‐cadherin, Snail, and vimentin, which are partial EMT markers promoting stemness and resistance to apoptosis. In addition, increased expressions of Nanog, Oct3/4, survivin, and Bcl‐2 were observed. Although the molecules we studied have diverse effects on cellular regulation, our data emphasize obesity's multifaceted role in promoting and aggressing PC, notably affecting PCSC populations.

中文翻译：

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脂肪条件培养基的多方面影响：肥胖驱动的前列腺癌和癌症干细胞动力学的促进

肥胖是前列腺癌（PC）发生和进展的既定危险因素。本研究使用来自分化脂肪细胞的脂肪条件培养基 (ACM) 来评估其对 PC 发育和侵袭性的影响。由于 ACM 对分离 PC 干细胞 (PCSC) 影响的研究有限，我们还检查了 CD44+PCSC。ACM 显着促进正常前列腺上皮细胞和 LNCaP 细胞中白介素-1β (IL-1β)、IL-6 和 IL-8 的产生。它还增加了 PC3 和 CD44 中 IL-6 和 IL-8 的产生+LNCaP 细胞以及 CD44 中 IL-1β 和 IL-6 的产生+PC3细胞。这表明 ACM 诱导癌症和前列腺上皮细胞产生炎症细胞因子。此外，ACM 促进雄激素受体 (AR) 阴性 PC3 细胞、CD44+PC3 PCSC 和非恶性 RWPE 细胞，不影响 AR 阳性 LNCaP 细胞。此外，ACM 增强了 PC3 和 CD44 的侵袭和迁移潜力+PC3细胞。Western blot 分析表明 NF-κB 和 AKT 通路参与 ACM 诱导的 PC3 细胞增殖和 NF-κB 诱导的 PCSC 增殖。在 ACM 处理的 PC3 细胞中，E-钙粘蛋白下调，而 N-钙粘蛋白、Snail、波形蛋白、纤连蛋白和 Twist 上调，表明 ACM 通过经典的上皮间质转化 (EMT) 途径诱导侵袭。作为对 ACM 的反应，PCSC 表现出 E-钙粘蛋白、Snail 和波形蛋白表达增加，这些是促进干性和抗凋亡的部分 EMT 标志物。此外，还观察到 Nanog、Oct3/4、survivin 和 Bcl-2 的表达增加。尽管我们研究的分子对细胞调节有不同的影响，但我们的数据强调了肥胖在促进和攻击 PC 方面的多方面作用，特别是影响 PCSC 群体。