Department of Medical Biology, School of Medicine, Trakya University, Balkan Campus, Edirne, Türkiye.
Department of Medical Biochemistry, School of Medicine, Trakya University, Balkan Campus, Edirne, Türkiye.
Cell Biochem Funct. 2024 Mar;42(2):e3979. doi: 10.1002/cbf.3979.
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.
肥胖是前列腺癌（PC）发生和进展的既定危险因素。本研究使用分化脂肪细胞的脂肪细胞条件培养基（ACM）来评估其对 PC 发展和侵袭性的影响。由于关于 ACM 对分离的 PC 干细胞（PCSCs）影响的研究有限，我们还检查了 CD44 PCSCs。ACM 显著增加了正常前列腺上皮细胞和 LNCaP 细胞中白细胞介素-1β（IL-1β）、IL-6 和 IL-8 的产生。它还增加了 PC3 和 CD44 LNCaP 细胞中 IL-6 和 IL-8 的产生，以及 CD44 PC3 细胞中 IL-1β 和 IL-6 的产生。这表明 ACM 诱导了癌症和前列腺上皮细胞中炎症细胞因子的产生。此外，ACM 促进了雄激素受体（AR）阴性 PC3 细胞、CD44 PC3 PCSCs 和非恶性 RWPE 细胞的增殖，而对 AR 阳性 LNCaP 细胞没有影响。此外，ACM 增强了 PC3 和 CD44 PC3 细胞的侵袭和迁移能力。Western blot 分析表明，NF-κB 和 AKT 途径参与了 ACM 诱导的 PC3 细胞增殖，而 NF-κB 则参与了 PCSCs。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 通过经典上皮间质转化（EMT）途径诱导侵袭。对 ACM 做出反应后，PCSCs 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。虽然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侵袭 PC 方面的多方面作用，特别是对 PCSC 群体的影响。
