Tryptophan metabolism along the kynurenine and serotonin pathways reveals substantial differences in colon and rectal cancer

Introduction Induction of tryptophan (TRP) catabolism is an adaptation mechanism to restrict excessive acute immune response in tissues. In the tumour microenvironment, TRP catabolism’s dysregulation plays an important role in local antitumour immune response suppression. Aim We investigated changes in the plasma concentrations of TRP and its metabolites in a cohort of colorectal cancer (CRC) patients at different tumour stages and in subjects at risk of developing CRC. TRP metabolites were assessed along kynurenine and serotonin pathways, and the activity of involved enzymes and their tissue expression were monitored. Method Plasmatic levels of tryptophan metabolites were quantified in 80 patients’ plasma samples by means of High-Pressure Liquid Chromatography coupled to UltraViolet/Fluorescence Detectors (HPLC-UV/FD), after a simple dilution step. Tissue IDO1 gene expression during to the adenoma-carcinoma sequence and samples were obtained from formalin-fixed and paraffin-embedded (FFPE) normal colon and tumour tissues from a subset of patients (n = 21). Results Altered TRP concentrations were detected in plasma samples concomitant to pre-cancerous lesion and persisted during the adenoma-carcinoma transition. Moreover, the anatomical site of cancer lesions (colon or rectum) strongly influences the TRP metabolic profiles. Colon cancer patients exhibited increased TRP catabolism with respect to those affected by rectal cancer, suggesting that TRP’s metabolism alterations play an important role in the onset and progression of colon cancer, but not in those of rectal cancer..

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Metabolomics - 13(2017), 12 vom: 29. Okt.

Sprache:

Englisch

Beteiligte Personen:

Crotti, S. [VerfasserIn]
D’Angelo, E. [VerfasserIn]
Bedin, C. [VerfasserIn]
Fassan, M. [VerfasserIn]
Pucciarelli, S. [VerfasserIn]
Nitti, D. [VerfasserIn]
Bertazzo, A. [VerfasserIn]
Agostini, M. [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

BKL:

42.15$jZellbiologie

Themen:

Biomarkers
Colorectal cancer
IDO
TPH
Tryptophan

Anmerkungen:

© Springer Science+Business Media, LLC 2017

doi:

10.1007/s11306-017-1288-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2084850134

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