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Altered tryptophan metabolism in human meningioma |
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| Authors: | Noble Kumar Talari Manas Panigrahi Sailaja Madigubba Sundaram Challa Prakash Babu Phanithi |
| Affiliation: | 1. Life Sciences Group, Bio-Rad Laboratories, Mississauga, ON, Canada 2. Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada 3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 4. The Centre for Applied Genomics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada 5. McGill University Health Centre, Montreal Neurological Hospital, Montreal, QC, Canada 6. Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada 7. Division of Neurosurgery and Department of Surgery, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada |
| Abstract: | Meningiomas are the neoplasms that arise from the arachnoid cells of the meninges. It was reported that cancer cells escape from immune system through the metabolism of an aromatic essential amino acid tryptophan (TRP) via Kynurenine (KYN) pathway. However, the role of TRP metabolites such as, 5-Hydroxy tryptophan (5-HTP), 5-Hydroxy tryptamine (5-HT), N-acetyl serotonin (NAS), Melatonin (MEL), KYN, N-acetyl tryptamine, 5-Hydroxy indole acetic acid (5-HIAA) and 5-Methoxy indole acetic acid is not yet evaluated in human meningioma. Therefore, in the current study we have evaluated the levels of TRP and its metabolites in the progression of human meningioma using tumor biopsy samples and autopsy control meninges with Reverse Phase-HPLC. We here report that TRP metabolism favors towards KYN pathway in human meningioma and it could be due to increased indoleamine 2,3-dioxygenase 2 levels as we found its m-RNA levels to be up regulated in human meningioma. We observed significant increase in KYN and 5HIAA levels and significant decrease in TRP, 5-HTP, 5-HT, NAS and MEL levels in meningioma compared to control meninges. Since TRP metabolites regulate inducible nitric oxide synthase (INOS) gene expression and thereby nitric oxide (NO) production, we have also evaluated the INOS and NO levels. The INOS and NO levels were up regulated in human meningioma. The present data corroborates with existing data on TRP metabolism in tumor progression and may serve to target TRP metabolism as a therapeutic intervention. |
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