Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer

Prostate cancer (PCa) is the second most prevalent malignancy in Western countries and the fifth leading cause of cancer-related death in men. The risk factors for PCa include obesity, age, and family history. Visceral fat has been linked to PCa risk, which has prompted researchers to investigate the influence of body composition and fat distribution on PCa prognosis. This study investigated the correlation between the composition of pelvic adipose tissue (PAT) and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, we prepared a periprostatic adipose tissue (PPAT)-conditioned medium (CM) to determine the influence of the PPAT secretome on the pathophysiology of PCa. This study included 60 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, and magnetic resonance imaging scans were analyzed, and body compositions were calculated to identify the correlations between adipose tissue volume and clinical PCa aggressiveness. CM was prepared using PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its influence was investigated using the PCa cell lines C4-2 and LNCaP and the prostate epithelial cell line PZ-HPV-7. Cell proliferation assays and RNA sequencing were performed. The initial prostate-specific antigen level was significantly correlated with pelvic and perirectal adipose tissue volumes. PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cells proliferated was significantly slower when cultured in PPAT-CM compared with when cultured in control- and PVAT-CM. RNA sequencing revealed that immune responses and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells. The cytokines or other secreted factors in PPAT-CM induced PCa cell apoptosis. This in vitro study revealed that the PPAT secretome inhibits PCa cells proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa. Overall design: RNA-Seq was performed to enable a comparison of the RNA expression between cells cultured in control-CM, PPAT-CM, or PVAT-CM.

前列腺癌（Prostate cancer, PCa）是西方国家第二大高发恶性肿瘤，同时也是男性癌症相关死亡的第五大主要诱因。前列腺癌的危险因素包括肥胖、年龄及家族遗传史。已有研究证实内脏脂肪与前列腺癌风险存在关联，这促使研究者们探索身体成分与脂肪分布对前列腺癌预后的影响。
本研究旨在探讨盆腔脂肪组织（pelvic adipose tissue, PAT）组成与前列腺癌侵袭性的关联，以明确该组织在前列腺癌进展中发挥的作用。此外，我们制备了前列腺周围脂肪组织（periprostatic adipose tissue, PPAT）条件培养基（conditioned medium, CM），用以探究PPAT分泌组对前列腺癌病理生理过程的影响。
本研究共纳入60例接受机器人辅助根治性前列腺切除术的局限性前列腺癌患者。研究人员收集患者病历资料，分析其磁共振成像扫描结果，并计算身体成分参数，以明确脂肪组织体积与前列腺癌临床侵袭性之间的相关性。
另外，我们收集了25例患者术中获取的前列腺周围脂肪组织与膀胱周围脂肪组织（perivesical adipose tissue, PVAT）来制备条件培养基，并采用前列腺癌细胞系C4-2、LNCaP及前列腺上皮细胞系PZ-HPV-7，探究该条件培养基的生物学影响。实验过程中开展了细胞增殖检测与RNA测序分析。
研究结果显示：初始前列腺特异性抗原（prostate-specific antigen, PSA）水平与盆腔及直肠周围脂肪组织体积呈显著相关；伴肿瘤包膜外扩展的患者，其PPAT体积显著更高。与对照组培养基及PVAT-CM培养环境相比，PPAT-CM培养的前列腺癌细胞增殖速度显著减慢。RNA测序结果表明，PPAT-CM培养的细胞中富集了免疫应答、细胞死亡及凋亡通路。进一步分析发现，PPAT-CM中的细胞因子或其他分泌因子可诱导前列腺癌细胞发生凋亡。
本体外研究证实，PPAT分泌组可通过激活免疫应答、促进癌细胞凋亡来抑制前列腺癌细胞增殖，该机制可能在前列腺癌早期阶段充当一线防御机制。
整体实验设计：本研究开展RNA测序，以比较分别在对照-CM、PPAT-CM及PVAT-CM中培养的细胞的RNA表达水平。