title: Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.
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.
authors.affiliation: Gastrointestinal and Hepatobiliary Malignancies Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: Xin
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Hari
authors.forename: John E
authors.initials: JE
authors.lastname: Mullinax
authors.forename: Chenwi M
authors.initials: CM
authors.lastname: Ambe
authors.forename: Tomotake
authors.initials: T
authors.lastname: Koizumi
authors.forename: Satyajit
authors.initials: S
authors.lastname: Ray
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Anderson
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Wiegand
authors.forename: Susan H
authors.initials: SH
authors.lastname: Garfield
authors.forename: Snorri S
authors.initials: SS
authors.lastname: Thorgeirsson
authors.forename: Itzhak
authors.initials: I
authors.lastname: Avital
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000378:metabolism; D013194:Staining and Labeling