Proline Metabolism in Malignant Gliomas: A Systematic Literature Review

SIMPLE SUMMARY: Studies of various types of cancers have found proline metabolism to be a key player in tumor development, involved in basic metabolic pathways, regulating cell proliferation, survival, and signaling. Here, we systematically searched the literature to find data on proline metabolism in malignant glial tumors. Despite limited availability, existing studies have found several ways in which proline metabolism may affect the development of gliomas, involving the maintenance of redox balance, providing essential glutamate, and affecting major signaling pathways. Metabolomic profiling has revealed the importance of proline as a link to basic cell metabolic cycles and shown it to be correlated with overall survival. Emerging knowledge on the role of proline in general oncology encourages further studies on malignant gliomas. ABSTRACT: Background: Proline has attracted growing interest because of its diverse influence on tumor metabolism and the discovery of the regulatory mechanisms that appear to be involved. In contrast to general oncology, data on proline metabolism in central nervous system malignancies are limited. Materials and Methods: We performed a systematic literature review of the MEDLINE and EMBASE databases according to PRISMA guidelines, searching for articles concerning proline metabolism in malignant glial tumors. From 815 search results, we identified 14 studies pertaining to this topic. Results: The role of the proline cycle in maintaining redox balance in IDH-mutated gliomas has been convincingly demonstrated. Proline is involved in restoring levels of glutamate, the main glial excitatory neurotransmitter. Proline oxidase influences two major signaling pathways: p53 and NF- κB. In metabolomics studies, the metabolism of proline and its link to the urea cycle was found to be a prognostic factor for survival and a marker of malignancy. Data on the prolidase concentration in the serum of glioblastoma patients are contradictory. Conclusions: Despite a paucity of studies in the literature, the available data are interesting enough to encourage further research, especially in terms of extrapolating what we have learned of proline functions from other neoplasms to malignant gliomas.