{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T09:11:45Z","timestamp":1778663505049,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Enhanced degradation of tryptophan (Trp) and thus decreased plasma Trp levels are common in several types of cancers. Although it is well known that Trp catabolism is induced in the tumor microenvironment by the enzymes expressed in cancer cells, immune cells, or both, few studies have examined systemic Trp catabolism in cancer pathophysiology. The present study aimed to evaluate Trp catabolism in both tumor and peripheral tissues using tumor\u2010engrafted Copenhagen rats that were s.c. inoculated with AT\u20102 rat prostate cancer cells negative for expression of Trp catabolic enzymes. Liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS) metabolomics showed significantly decreased plasma Trp levels in AT\u20102 engrafted rats, accompanied by increased kynurenine\/Trp ratios in spleen and thymus and serotonin levels in liver and thymus. Quantitative PCR and enzymatic activity assays showed indoleamine\u20102, 3\u2010dioxygenase, an inducible enzyme that catalyzes Trp to kynurenine, was increased in tumor tissues, whereas tryptophan\u20102,3\u2010dioxygenase, a major Trp catabolic enzyme that regulates systemic level of Trp, tended to be increased in the liver of AT\u20102 engrafted rats. Furthermore, tryptophan hydroxylase\u20101 (TPH1), an enzyme that catalyzes the reaction of Trp to serotonin, was significantly increased in liver and spleen of AT\u20102 engrafted rats. Further histochemical analysis revealed that the induction of TPH1 in the liver could be attributed to infiltration of mast cells. A similar phenomenon was observed with nonneoplastic liver samples from colorectal cancer patients. These results suggested that Trp catabolism toward serotonin synthesis might be induced in peripheral remote tissues in cancer, which could have a pathophysiological effect on cancer.<\/jats:p>","DOI":"10.1111\/cas.14333","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T08:25:41Z","timestamp":1580372741000},"page":"1218-1227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Induction of tryptophan hydroxylase in the liver of s.c. tumor model of prostate cancer"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-0113","authenticated-orcid":false,"given":"Asami","family":"Hagiwara","sequence":"first","affiliation":[{"name":"Material &amp; Technology Solutions Labs Research Institute for Bioscience Products &amp; Fine Chemicals Ajinomoto Co., Inc Kawasaki City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyasu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Molecular Pathology and Genetics Divisiosn Kanagawa Cancer Center Research Institute Kanagawa Cancer Center Yokohama City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rumi","family":"Nishimoto","sequence":"additional","affiliation":[{"name":"Material &amp; Technology Solutions Labs Research Institute for Bioscience Products &amp; Fine Chemicals Ajinomoto Co., Inc Kawasaki City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Ueno","sequence":"additional","affiliation":[{"name":"Material &amp; Technology Solutions Labs Research Institute for Bioscience Products &amp; Fine Chemicals Ajinomoto Co., Inc Kawasaki City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Molecular Pathology and Genetics Divisiosn Kanagawa Cancer Center Research Institute Kanagawa Cancer Center Yokohama City Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.02.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf9794"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1178646917691938"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-0569"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm934"},{"key":"e_1_2_10_7_1","first-page":"699","article-title":"Differential patterns of serum biomarkers of immune activation in human T\u2010cell lymphotropic virus type I\u2010associated myelopathy\/tropical spastic paraparesis, and adult T\u2010cell leukemia\/lymphoma","volume":"5","author":"Giusti RM","year":"1996","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2009.05.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000096906"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.10.033"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600336"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i13.3592"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024143"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-007-0191-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20000601)43:4<295::AID-PROS9>3.0.CO;2-W"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990090306"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.4026"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2016.11.068"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145713001673"},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1016\/S0021-9258(19)85644-2","article-title":"Tryptophan hydroxylase. 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