Identification of Cancer Stem Cells in Human Gastrointestinal Carcinoid and Neuroendocrine Tumors

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dc.contributor.author Gaur, Puja
dc.contributor.author Sceusi, Eric
dc.contributor.author Samuel, Shaija
dc.contributor.author Xia, Ling
dc.contributor.author Zhou, Yunfei
dc.contributor.author Lu, Jia
dc.contributor.author Tozzi, Federico
dc.contributor.author Lopez-Berestein, Gabriel
dc.contributor.author Vivas-Mejia, Pablo
dc.contributor.author Fleming, Jason
dc.contributor.author Abdalla, Eddie
dc.contributor.author Curley, Steven
dc.contributor.author Vauthey, Jean-Nicolas
dc.contributor.author Sood, Anil
dc.contributor.author Yao, James
dc.contributor.author Ellis, Lee
dc.date.accessioned 2015-11-19T14:05:25Z
dc.date.available 2015-11-19T14:05:25Z
dc.date.copyright 2011
dc.date.issued 2015-11-19
dc.identifier.issn 0016-5085 en_US
dc.identifier.uri http://hdl.handle.net/10725/2635
dc.description.abstract Background & Aims Metastatic gastrointestinal neuroendocrine tumors (NETs) frequently are refractory to chemotherapy. Chemoresistance in various malignancies has been attributed to cancer stem cells (CSCs). We sought to identify gastrointestinal neuroendocrine CSCs (N-CSCs) in surgical specimens and a NET cell line and to characterize novel N-CSC therapeutic targets. Methods Human gastrointestinal NETs were evaluated for CSCs using the Aldefluor (Stemcell Technologies, Vancouver, Canada) assay. An in vitro, sphere-forming assay was performed on primary NET cells. CNDT2.5, a human midgut carcinoid cell line, was used for in vitro (sphere-formation) and in vivo (tumorigenicity assays) CSC studies. N-CSC protein expression was characterized using Western blotting. In vivo, systemic short interfering RNA administration targeted Src. Results By using the Aldefluor assay, aldehyde dehydrogenase–positive (ALDH+) cells comprised 5.8% ± 1.4% (mean ± standard error of the mean) of cells from 19 patient samples. Although many primary cell lines failed to grow, CNDT96 ALDH+ cells formed spheres in anchorage-independent conditions, whereas ALDH- cells did not. CNDT2.5 ALDH+ cells formed spheres, whereas ALDH- cells did not. In vivo, ALDH+ CNDT2.5 cells generated more tumors, with shorter latency than ALDH- or sham-sorted cells. Compared with non-CSCs, ALDH+ cells demonstrated increased expression of activated Src, Erk, Akt, and mammalian target of rapamycin (mTOR). In vivo, anti-Src short interfering RNA treatment of ALDH+ tumors reduced tumor mass by 91%. Conclusions CSCs are present in NETs, as shown by in vitro sphere formation and in vivo tumorigenicity assays. Src was activated in N-CSCs and represents a potential therapeutic target in gastrointestinal NETs. en_US
dc.language.iso en en_US
dc.title Identification of Cancer Stem Cells in Human Gastrointestinal Carcinoid and Neuroendocrine Tumors en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 201100945 en_US
dc.author.woa N/A en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Gastroenterology en_US
dc.journal.volume 141 en_US
dc.journal.issue 5 en_US
dc.article.pages 1728-1737 en_US
dc.identifier.ctation Gaur, P., Sceusi, E. L., Samuel, S., Xia, L., Fan, F., Zhou, Y., ... & Ellis, L. M. (2011). Identification of cancer stem cells in human gastrointestinal carcinoid and neuroendocrine tumors. Gastroenterology, 141(5), 1728-1737. en_US
dc.author.email eddie.abdalla@lau.edu.lb
dc.identifier.url http://www.sciencedirect.com/science/article/pii/S0016508511010705

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