Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue.

Autor: Sawicka MM; Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok, Poland., Sawicki K; Department of Neurosurgery, Medical University of Bialystok, Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland., Jadeszko M; Department of Neurosurgery, Medical University of Bialystok, Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland., Bielawska K; Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok, Poland., Supruniuk E; Department of Physiology, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland., Reszeć J; Department of Medical Pathomorphology, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland., Prokop-Bielenia I; Department of Medicinal Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok, Poland., Polityńska B; Department of Psychology and Philosophy, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland., Jadeszko M; Department of Vascular Surgery and Transplantation, Medical University of Bialystok, Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland., Rybaczek M; Department of Neurosurgery, Medical University of Bialystok, Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland., Latoch E; Department of Pediatric Oncology and Hematology, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland., Gorbacz K; Department of Neurosurgery, Medical University of Bialystok, Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland., Łysoń T; Department of Neurosurgery, Medical University of Bialystok, Skłodowskiej-Curie 24A, 15-276 Bialystok, Poland., Miltyk W; Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bialystok, Poland.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Jan 21; Vol. 16 (2). Date of Electronic Publication: 2024 Jan 21.
DOI: 10.3390/cancers16020456
Abstrakt: 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), Δ 1 -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.
Databáze: MEDLINE
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