Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

Stem Cells
Hong-Wu XinItzhak Avital

Abstract

Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment.

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Citations

Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yang Hoon HuhJames L Sherley
Dec 4, 2012·Stem Cells and Development·Jang Pyo ParkBrian W Booth
Apr 2, 2013·Stem Cells and Development·Jiang-Jie DuanShi-Cang Yu
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May 21, 2019·Oncotarget·Paloma Honrubia-GómezCarmen Ramirez-Castillejo
Aug 5, 2020·Journal of Hematology & Oncology·Yingying WangHong-Wu Xin
Aug 15, 2020·Frontiers in Oncology·Wen-Qi CaiHong-Wu Xin
Jun 4, 2020·Investigational New Drugs·Zi-Wen HanHong-Wu Xin
Aug 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Lei LiXin-Yuan Guan
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Dec 23, 2020·JCI Insight·Masahiro HitomiJustin D Lathia
Jul 27, 2021·Frontiers in Genetics·Shao-Li HuangHong-Wu Xin

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