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Cancer Stem Cells
Article first published online: 22 MAR 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 4, pages 591–598, April 2012
How to Cite
Xin, H.-W., Hari, D. M., Mullinax, J. E., Ambe, C. M., Koizumi, T., Ray, S., Anderson, A. J., Wiegand, G. W., Garfield, S. H., Thorgeirsson, S. S. and Avital, I. (2012), Tumor-Initiating Label-Retaining Cancer Cells in Human Gastrointestinal Cancers Undergo Asymmetric Cell Division. STEM CELLS, 30: 591–598. doi: 10.1002/stem.1061
Author contributions: H.-W.X: concept and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; D.M.H., J.E.M., C.M.A., A.J.A., G.W.W., and S.H.G.: collection and assembly of data; T.K. and S.R.: manuscript writing; S.S.T.: data analysis and interpretation and manuscript writing; I.A: concept and design, data analysis and interpretation, manuscript writing, and final approval of manuscript. H.-W.X. and D.M.H. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS February 13, 2012.
- Issue published online: 22 MAR 2012
- Article first published online: 22 MAR 2012
- Accepted manuscript online: 13 FEB 2012 04:43PM EST
- Manuscript Accepted: 29 JAN 2012
- Manuscript Received: 16 DEC 2011
- NIH/National Cancer Institute
- Adult stem cells;
- Cancer stem cells;
- Asymmetric cell division;
- Cairns immortal strand hypothesis;
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. STEM CELLS2012; 30:591–598