title: Precancerous stem cells have the potential for both benign and malignant differentiation.
abstract: Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors-namely, precancerous stem cells (pCSCs) -have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers.
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, Ohio, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Rulong
authors.initials: R
authors.lastname: Shen
authors.forename: Yin
authors.initials: Y
authors.lastname: Ye
authors.forename: Xin-An
authors.initials: XA
authors.lastname: Pu
authors.forename: Xingluo
authors.initials: X
authors.lastname: Liu
authors.forename: Wenrui
authors.initials: W
authors.lastname: Duan
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Jason
authors.initials: J
authors.lastname: Zimmerer
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Larry C
authors.initials: LC
authors.lastname: Lasky
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
authors.forename: Danilo
authors.initials: D
authors.lastname: Perrotti
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.forename: Satomi
authors.initials: S
authors.lastname: Kuramochi-Miyagawa
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Yates
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.forename: Haifan
authors.initials: H
authors.lastname: Lin
authors.forename: Sanford H
authors.initials: SH
authors.lastname: Barsky
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Gao
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology* / Q000528:radiation effects; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002478:Cells, Cultured; D003463:Cues; D004777:Environment; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000473:pathology; D008099:Liver / Q000473:pathology; D051379:Mice; D010641:Phenotype; D011230:Precancerous Conditions / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000473:pathology*
chemical_list: D034741:RNA, Small Interfering