{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:41:54Z","timestamp":1790606514989,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["PI19\/01422"],"award-info":[{"award-number":["PI19\/01422"]}]},{"name":"European Union","award":["PI19\/01422"],"award-info":[{"award-number":["PI19\/01422"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer cachexia is a multifactorial syndrome that interferes with treatment and reduces the quality of life and survival of patients. Currently, there is no effective treatment or biomarkers, and pathophysiology is not clear. Our group reported alterations on tryptophan metabolites in cachectic patients, so we aim to investigate the role of tryptophan using two cancer-associated cachexia syngeneic murine models, melanoma B16F10, and pancreatic adenocarcinoma that is KPC-based. Injected mice showed signs of cancer-associated cachexia as reduction in body weight and raised spleen weight, MCP1, and carbonilated proteins in plasma. CRP and Myostatin also increased in B16F10 mice. Skeletal muscle showed a decrease in quadriceps weight and cross-sectional area (especially in B16F10). Higher expression of atrophy genes, mainly Atrogin1, was also observed. Plasmatic tryptophan levels in B16F10 tumor-bearing mice decreased even at early steps of tumorigenesis. In KPC-injected mice, tryptophan fluctuated but were also reduced and in cachectic patients were significantly lower. Treatment with 1-methyl-tryptophan, an inhibitor of tryptophan degradation, in the murine models resulted in the restoration of plasmatic tryptophan levels and an improvement on splenomegaly and carbonilated proteins levels, while changes in plasmatic inflammatory markers were mild. After the treatment, CCR2 expression in monocytes diminished and lymphocytes, Tregs, and CD8+, were activated (seen by increased in CD127 and CD25 expression, respectively). These immune cell changes pointed to an improvement in systemic inflammation. While treatment with 1-MT did not show benefits in terms of muscle wasting and atrophy in our experimental setting, muscle functionality was not affected and central nuclei fibers appeared, being a feature of regeneration. Therefore, tryptophan metabolism pathway is a promising target for inflammation modulation in cancer-associated cachexia.<\/jats:p>","DOI":"10.3390\/ijms241613005","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:53:31Z","timestamp":1692608011000},"page":"13005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tryptophan Modulation in Cancer-Associated Cachexia Mouse Models"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7617-6681","authenticated-orcid":false,"given":"M. Teresa","family":"Agull\u00f3-Ortu\u00f1o","sequence":"first","affiliation":[{"name":"Laboratory of Clinical and Translational Oncology, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"},{"name":"Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO), 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Centre on Oncology\u2014CIBERONC, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Nursing, Facultad de Fisioterapia y Enfermer\u00eda, Universidad de Castilla La-Mancha (UCLM), 45071 Toledo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1535-9062","authenticated-orcid":false,"given":"Esther","family":"Mancebo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitario 12 de Octubre, Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Grau","sequence":"additional","affiliation":[{"name":"Animal Facility, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"N\u00fa\u00f1ez Sobrino","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre, Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Paz-Ares","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Translational Oncology, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"},{"name":"Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncol\u00f3gicas (CNIO), 28029 Madrid, Spain"},{"name":"Biomedical Research Networking Centre on Oncology\u2014CIBERONC, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre, Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"},{"name":"Medicine Department, Facultad de Medicina y Cirug\u00eda, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"L\u00f3pez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre, Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-2267","authenticated-orcid":false,"given":"Marta","family":"Fl\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Translational Oncology, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (Imas12), Av. C\u00f3rdoba s\/n, 28041 Madrid, Spain"},{"name":"Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Pozuelo de Alarc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. 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