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Cancer-initiating cells in human pancreatic cancer organoids are maintained by interactions with endothelial cells

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dc.contributor.authorChoi, Jae-Il-
dc.contributor.authorJang, Sung Ill-
dc.contributor.authorHong, Jaehyun-
dc.contributor.authorKim, Chul Hoon-
dc.contributor.authorKwon, Soon Sung-
dc.contributor.authorPark, Joon Seong-
dc.contributor.authorLim, Jong-Baeck-
dc.contributor.author최재일-
dc.date.accessioned2021-03-31T01:36:15Z-
dc.date.available2021-03-31T01:36:15Z-
dc.date.created2021-02-22-
dc.date.issued2021-02-
dc.identifier.issn0304-3835-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/181845-
dc.description.abstractPancreatic ductal adenocarcinoma (PDAC) shows poor prognosis and high malignancy due to the presence of cancer-initiating cells (CICs) and characteristics of the tumor microenvironment (TME). Organoids are useful for studying PDAC, and establishing organoids is dependent on stem cell growth factors, including Wnt signaling. Herein, using a conventional organoid culture system, we demonstrated that CD44(+)CD24(+) and CD44(+) CD24(+)EpCAM(+) CICs were enriched >65% in a PDAC patient-derived organoid. CICs expressing CD44 formed lumen structures by gathering into circles. Additionally, organoid-derived CD44(-) cancer cells were capable of organoid re-formation and could be re-programed as CD44-expressing CICs in the organoid culture system. To mimic a TME absent artificial stem cell growth factors, a PDAC organoid with vascular niche was established. CICs in the PDAC tumor organoid were maintained by paracrine effects and direct interactions with endothelial cells. Interestingly, CD44(+) cells in PDAC tumor tissue were detected primarily in the vascular niche. Inhibiting both Wnt and Notch signaling in endothelial cells suppressed organoid formation and the maintenance of CD24(+)CD44(+) CICs. Collectively, our results suggest that PDAC patient-derived organoids maintain CICs by interacting with endothelial cells via Wnt and Notch pathways.-
dc.language영어-
dc.publisherELSEVIER IRELAND LTD-
dc.relation.isPartOfCANCER LETTERS-
dc.titleCancer-initiating cells in human pancreatic cancer organoids are maintained by interactions with endothelial cells-
dc.typeArticle-
dc.contributor.googleauthorChoi, Jae-Il-
dc.contributor.googleauthorJang, Sung Ill-
dc.contributor.googleauthorHong, Jaehyun-
dc.contributor.googleauthorKim, Chul Hoon-
dc.contributor.googleauthorKwon, Soon Sung-
dc.contributor.googleauthorPark, Joon Seong-
dc.contributor.googleauthorLim, Jong-Baeck-
dc.identifier.doi10.1016/j.canlet.2020.10.012-
dc.relation.journalcodeJ00448-
dc.identifier.eissn1872-7980-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0304383520305280-
dc.subject.keywordHuman cancer organoid-
dc.subject.keywordCancer stem cells-
dc.subject.keywordVascular niche-
dc.subject.keywordTumor microenvironment-
dc.subject.keywordCancer plasticity-
dc.contributor.affiliatedAuthorChoi, Jae-Il-
dc.contributor.affiliatedAuthorJang, Sung Ill-
dc.contributor.affiliatedAuthorKim, Chul Hoon-
dc.contributor.affiliatedAuthorKwon, Soon Sung-
dc.contributor.affiliatedAuthorPark, Joon Seong-
dc.contributor.affiliatedAuthorLim, Jong-Baeck-
dc.identifier.scopusid2-s2.0-85096376110-
dc.identifier.wosid000600677200004-
dc.citation.titleCANCER LETTERS-
dc.citation.volume498-
dc.citation.startPage42-
dc.citation.endPage53-
dc.identifier.bibliographicCitationCANCER LETTERS, Vol.498 : 42-53, 2021-02-
dc.identifier.rimsid67567-
dc.type.rimsART-
dc.description.journalClass1-
dc.description.journalClass1-
dc.subject.keywordAuthorHuman cancer organoid-
dc.subject.keywordAuthorCancer stem cells-
dc.subject.keywordAuthorVascular niche-
dc.subject.keywordAuthorTumor microenvironment-
dc.subject.keywordAuthorCancer plasticity-
dc.subject.keywordPlusSTEM-CELLS-
dc.subject.keywordPlusNICHE-
dc.type.docTypeArticle-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalWebOfScienceCategoryOncology-
dc.relation.journalResearchAreaOncology-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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