Induction of tryptophan hydroxylase in the liver of s.c. tumor model of prostate cancer

• DOI: 10.1111/cas.14333
• Publication Date: 2020-01-30T08:25:41Z
• Authors: Asami Hagiwara; Yoshiyasu Nakamura; Rumi Nishimoto; Satoko Ueno; Yohei Miyagi
• Keywords: Catabolism; Indoleamine 2,3-dioxygenase; Tryptophan hydroxylase

Enhanced degradation of tryptophan (Trp) and thus decreased plasma Trp levels are common in several types cancers. Although it is well known that catabolism induced the tumor microenvironment by enzymes expressed cancer cells, immune or both, few studies have examined systemic pathophysiology. The present study aimed to evaluate both peripheral tissues using tumor-engrafted Copenhagen rats were s.c. inoculated with AT-2 rat prostate cells negative for expression catabolic enzymes. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics showed significantly engrafted rats, accompanied increased kynurenine/Trp ratios spleen thymus serotonin liver thymus. Quantitative PCR enzymatic activity assays indoleamine-2, 3-dioxygenase, an inducible enzyme catalyzes kynurenine, was tissues, whereas tryptophan-2,3-dioxygenase, a major regulates level Trp, tended be rats. Furthermore, hydroxylase-1 (TPH1), reaction serotonin, Further histochemical analysis revealed induction TPH1 could attributed infiltration mast cells. A similar phenomenon observed nonneoplastic samples from colorectal patients. These results suggested toward synthesis might remote cancer, which pathophysiological effect on cancer.