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

Hong Wu Xin, Danielle M. Hari, John E. Mullinax, Chenwi M. Ambe, Tomotake Koizumi, Satyajit Ray, Andrew J. Anderson, Gordon W. Wiegand, Susan H. Garfield, Snorri S. Thorgeirsson, Itzhak Avital

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish
Pages (from-to)591-598
Number of pages8
JournalStem Cells
Volume30
Issue number4
DOIs
StatePublished - 1 Apr 2012
Externally publishedYes

Keywords

  • Adult stem cells
  • Asymmetric cell division
  • Cairns immortal strand hypothesis
  • Cancer stem cells
  • Liver
  • Self-renewal

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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