{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:51:42Z","timestamp":1787496702265,"version":"build-2736575974"},"reference-count":75,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The majority of patients with pancreatic cancer develops cachexia. The mechanisms underlying cancer cachexia development and progression remain elusive, although tumour\u2010derived factors are considered to play a major role. Pancreatic tumour organoids are\n in vitro<\/jats:italic>\n three\u2010dimensional organ\u2010like structures that retain many pathophysiological characteristics of the\n in vivo<\/jats:italic>\n tumour. We aimed to establish a pancreatic tumour organoid biobank from well\u2010phenotyped cachectic and non\u2010cachectic patients to enable identification of tumour\u2010derived factors driving cancer cachexia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Organoids were generated from tumour tissue of eight pancreatic cancer patients. A comprehensive pre\u2010operative patient assessment of cachexia\u2010related parameters including nutritional status, physical performance, body composition, and inflammation was performed. Tumour\u2010related and cachexia\u2010related characteristics of the organoids were analysed using histological stainings, targeted sequencing, and real\u2010time\u2013quantitative PCR. Cachexia\u2010related factors present in the circulation of the patients and in the tumour organoid secretome were analysed by enzyme\u2010linked immunosorbent assay.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The established human pancreatic tumour organoids presented typical features of malignancy corresponding to the primary tumour (i.e. nuclear enlargement, multiple nucleoli, mitosis, apoptosis, and mutated\n KRAS<\/jats:italic>\n and\/or\n TP53<\/jats:italic>\n ). These tumour organoids also expressed variable levels of many known cachexia\u2010related genes including interleukin\u20106 (\n IL\u20106<\/jats:italic>\n ),\n TNF\u2010\u03b1<\/jats:italic>\n ,\n IL\u20108<\/jats:italic>\n ,\n IL\u20101\u03b1<\/jats:italic>\n ,\n IL\u20101\u03b2<\/jats:italic>\n ,\n Mcp\u20101<\/jats:italic>\n ,\n GDF15<\/jats:italic>\n , and\n LIF<\/jats:italic>\n . mRNA expression of\n IL\u20101\u03b1<\/jats:italic>\n and\n IL\u20101\u03b2<\/jats:italic>\n was significantly reduced in organoids from cachectic vs. non\u2010cachectic patients (\n IL\u20101\u03b1<\/jats:italic>\n : \u22123.8\u2010fold,\n P<\/jats:italic>\n \u00a0=\u00a00.009, and\n IL\u20101\u03b2<\/jats:italic>\n : \u22124.7\u2010fold,\n P<\/jats:italic>\n \u00a0=\u00a00.004).\n LIF<\/jats:italic>\n ,\n IL\u20108<\/jats:italic>\n , and\n GDF15<\/jats:italic>\n mRNA expression levels were significantly higher in organoids from cachectic vs. non\u2010cachectic patients (\n LIF<\/jats:italic>\n : 1.6\u2010fold,\n P<\/jats:italic>\n \u00a0=\u00a00.003;\n IL\u20108<\/jats:italic>\n : 1.4\u2010fold,\n P<\/jats:italic>\n \u00a0=\u00a00.01;\n GDF15<\/jats:italic>\n : 2.3\u2010fold,\n P<\/jats:italic>\n \u00a0<\u00a00.001). In line with the\n GDF15<\/jats:italic>\n and\n IL\u20108<\/jats:italic>\n mRNA expression levels, tumour organoids from cachectic patients secreted more GDF15 and IL\u20108 compared with organoids from non\u2010cachectic patients (5.4 vs. 1.5\u00a0ng\/mL,\n P<\/jats:italic>\n \u00a0=\u00a00.01, and 7.4 vs. 1.3\u00a0ng\/mL,\n P<\/jats:italic>\n \u00a0=\u00a00.07, respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This novel human pancreatic tumour organoid biobank provides a valuable tool to increase our understanding of the mechanisms driving cancer cachexia. Our preliminary characterization of the secretome of these organoids supports their application in functional studies including conditioned medium approaches and\n in vivo<\/jats:italic>\n transplantation models.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.12627","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T10:08:20Z","timestamp":1602583700000},"page":"1509-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Generation and initial characterization of novel tumour organoid models to study human pancreatic cancer\u2010induced cachexia"],"prefix":"10.1002","volume":"11","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 Maastricht University Maastricht The Netherlands"},{"name":"NUTRIM School of Nutrition and Translational 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