{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:35:11Z","timestamp":1790094911488,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T00:00:00Z","timestamp":1706227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NUTRIM Graduate Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Patients with pancreatic cancer often suffer from cachexia and experience gastrointestinal symptoms that may be related to intestinal smooth muscle cell (SMC) dysfunction. We hypothesized that pancreatic tumor organoids from cachectic patients release factors that perturb the SMC\u2019s contractile characteristics. Human visceral SMCs were exposed to conditioned medium (CM) from the pancreatic tumor organoid cultures of cachectic (n = 2) and non-cachectic (n = 2) patients. Contractile proteins and markers of inflammation, muscle atrophy, and proliferation were evaluated by qPCR and Western blot. SMC proliferation and migration were monitored by live cell imaging. The Ki-67-positive cell fraction was determined in the intestinal smooth musculature of pancreatic cancer patients. CM from the pancreatic tumor organoids of cachectic patients did not affect IL-1\u03b2, IL-6, IL-8, MCP-1, or Atrogin-1 expression. However, CM reduced the \u03b1-SMA, \u03b3-SMA, and SM22-\u03b1 levels, which was accompanied by a reduced SMC doubling time and increased expression of S100A4, a Ca2+-binding protein associated with the synthetic SMC phenotype. In line with this, Ki-67-positive nuclei were increased in the intestinal smooth musculature of patients with a low versus high L3-SMI. In conclusion, patient-derived pancreatic tumor organoids release factors that compromise the contractile SMC phenotype and increase SMC proliferation. This may contribute to the frequently observed gastrointestinal motility problems in these patients.<\/jats:p>","DOI":"10.3390\/cancers16030542","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T10:54:27Z","timestamp":1706266467000},"page":"542","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pancreatic Tumor Organoid-Derived Factors from Cachectic Patients Disrupt Contractile Smooth Muscle Cells"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6812-2897","authenticated-orcid":false,"given":"Rianne D. W.","family":"Vaes","sequence":"first","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8106-6455","authenticated-orcid":false,"given":"Annemarie A.","family":"van Bijnen","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W. M. Olde","family":"Damink","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplant Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-8400","authenticated-orcid":false,"given":"Sander S.","family":"Rensen","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,26]]},"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. 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