Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ1-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted.
脯氨酸代谢在多种肿瘤中被证实具有重要作用，但其在胶质瘤中的功能认知仍较为有限，尽管该研究方向颇具前景。目前关于大脑中脯氨酸代谢的数据多基于早期研究。本研究旨在探讨世界卫生组织4级胶质瘤（GG4）在大脑环境中的脯氨酸代谢改变。研究共纳入20对样本，包括手术切除的肿瘤组织及未受累脑组织，这些样本均来自为抵达深部病灶而需进行部分脑切除的病例。通过检测脯氨酸氧化酶/脯氨酸脱氢酶（POX/PRODH）、Δ1-吡咯啉-5-羧酸还原酶（PYCR1/2/3）、脯氨酰肽酶（PEPD）及金属蛋白酶（MMP-2、MMP-9）的表达水平，同时测定脯氨酸及其相关代谢物浓度，发现与正常脑组织相比，GG4中POX/PRODH表达受到抑制，而PYCR1表达及PEPD、MMP-2和MMP-9活性显著上调。GG4组织中脯氨酸浓度升高达358%。由此首次证实GG4存在脯氨酸代谢重编程，呈现低POX/PRODH与高PYCR的特征模式。PEPD与MMPs的高活性与GG4胶原代谢增强及局部侵袭性特征相符。后续需进一步探究脯氨酸代谢改变与GG4微环境相互作用的分子机制。
Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue
肿瘤(癌症)患者之家