Department of Pathology, Bretonneau Hospital, CHU - University of Tours, Tours, France.
Inserm UMR U1069, Tours, France.
J Pathol. 2021 Oct;255(2):166-176. doi: 10.1002/path.5754. Epub 2021 Aug 7.
The prostate gland is surrounded by periprostatic adipose tissue (PPAT), which is believed to play a role in prostate cancer (PCa) progression. Cancer cells can take up lipids from the microenvironment and store them in lipid droplets (LDs). Fatty acids released from LDs are used by PCa cells as preferential metabolic fuels to provide energy and promote cancer progression. Recently, fatty acids have been associated with autophagy, a cellular recycling pathway. Lipophagy is a selective form of autophagy involved in LD degradation, the role of which in PCa progression remains unknown. Here, we explored markers of autophagy and lipophagy in human PCa tissues in correlation with factors of aggressiveness, and we evaluated the influence of PPAT adipocytes on autophagy and lipophagy. We analyzed markers of autophagy (p62, LC3), lipid droplets (PLIN and Oil Red O), androgen receptor (AR), proliferation (Ki67), and epithelial-mesenchymal transition (Zeb1) on 465 PCa samples. Co-cultures of PCa cell lines PC3 and 22RV1 with adipocytes isolated from patients' PPAT were used to analyze the influence of PPAT on autophagy and lipophagy in vitro. In human PCa tissues, we observed a correlation between markers of LD and those of autophagy, which are associated with clinical and biological factors of disease aggressiveness. In addition, PLIN staining was associated with AR expression. In locally advanced PCa, p62, LC3, and PLIN were increased in extraprostatic areas where cancer cells are in contact with PPAT. Co-culture of PCa cell lines with adipocytes decreased autophagy activity and increased LD flux in PC3 cells. These results suggest an active process of lipophagy in PCa, linked to disease aggressiveness, to the proximity of PPAT, and induced in vitro in co-culture with adipocytes. Lipophagy is therefore likely to be a crucial player in PCa progression. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
前列腺被前列腺周脂肪组织 (PPAT) 环绕，后者被认为在前列腺癌 (PCa) 进展中发挥作用。癌细胞可以从微环境中摄取脂质并将其储存在脂滴 (LD) 中。从 LD 释放的脂肪酸被 PCa 细胞用作首选代谢燃料，以提供能量并促进癌症进展。最近，脂肪酸与自噬有关，自噬是一种细胞回收途径。脂噬是 LD 降解中涉及的一种选择性自噬形式，其在 PCa 进展中的作用尚不清楚。在这里，我们探讨了与侵袭性相关的人类 PCa 组织中自噬和脂噬的标志物，并评估了 PPAT 脂肪细胞对自噬和脂噬的影响。我们分析了 465 个 PCa 样本中自噬标志物 (p62、LC3)、脂滴标志物 (PLIN 和油红 O)、雄激素受体 (AR)、增殖 (Ki67) 和上皮-间充质转化 (Zeb1)。使用从患者 PPAT 中分离的脂肪细胞对 PCa 细胞系 PC3 和 22RV1 进行共培养，以分析 PPAT 对体外自噬和脂噬的影响。在人类 PCa 组织中，我们观察到 LD 标志物与自噬标志物之间存在相关性，这些标志物与疾病侵袭性的临床和生物学因素相关。此外，PLIN 染色与 AR 表达相关。在局部晚期 PCa 中，p62、LC3 和 PLIN 在前列腺外区域增加，在这些区域，癌细胞与 PPAT 接触。PCa 细胞系与脂肪细胞共培养降低了 PC3 细胞的自噬活性并增加了 LD 通量。这些结果表明，脂噬在 PCa 中是一种活跃的过程，与疾病侵袭性、与 PPAT 的接近程度以及体外与脂肪细胞共培养有关。因此，脂噬很可能是 PCa 进展的关键因素。
