Altered tryptophan metabolism in human meningioma
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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.
KeywordsTryptophan Kynurenine Serotonin IDO Meningioma
This work was supported by grants from the CSIR, ICMR, DST, DBT and UPE. Department of Science and Technology [SB/EMEQ-257/2013, dt. 12 July 2013], Department of Biotechnology [BT/PR13111/MED/29/149/2009, dt. 24 June 2010] and University with Potential for Excellence—Phase II [UH/UGC/UPE-2/Interface Studies/Research Projects/B1.4] New Delhi, Govt. of India. The authors wish to acknowledge help of Dr. Janaki, Kurnool Medical College, Andhra Pradesh, India, for providing autopsy meninges for our study.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest.
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