title: Identification of cancer stem cells and a strategy for their elimination.
abstract: It has been established previously that up to 40% of mouse CD34(+) hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential.
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Evgenia V
authors.initials: EV
authors.lastname: Dolgova
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Alyamkina
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia; Novosibirsk State University; Novosibirsk, Russia.
authors.forename: Yaroslav R
authors.initials: YR
authors.lastname: Efremov
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Valeriy P
authors.initials: VP
authors.lastname: Nikolin
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia; Novosibirsk State University; Novosibirsk, Russia.
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Popova
authors.affiliation: Institute of Clinical Immunology; Siberian Branch of the Russian Academy of Medical Sciences; Novosibirsk, Russia.
authors.forename: Tamara V
authors.initials: TV
authors.lastname: Tyrinova
authors.affiliation: Novosibirsk State University; Novosibirsk, Russia.
authors.forename: Artem V
authors.initials: AV
authors.lastname: Kozel
authors.affiliation: Novosibirsk State University; Novosibirsk, Russia.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Minkevich
authors.affiliation: Novosibirsk State University; Novosibirsk, Russia.
authors.forename: Oleg M
authors.initials: OM
authors.lastname: Andrushkevich
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Evgeniy L
authors.initials: EL
authors.lastname: Zavyalov
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Romaschenko
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia; Novosibirsk State University; Novosibirsk, Russia.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Bayborodin
authors.affiliation: The State Research Center of Virology and Biotechnology VECTOR; Koltsovo, Russia.
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Taranov
authors.affiliation: The State Research Center of Virology and Biotechnology VECTOR; Koltsovo, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Omigov
authors.affiliation: Institute of Clinical Immunology; Siberian Branch of the Russian Academy of Medical Sciences; Novosibirsk, Russia.
authors.forename: Ekaterina Ya
authors.initials: EY
authors.lastname: Shevela
authors.affiliation: Novosibirsk Research Institute of Traumatology and Orthopaedics; Novosibirsk, Russia.
authors.forename: Vyacheslav V
authors.initials: VV
authors.lastname: Stupak
authors.affiliation: Novosibirsk Research Institute of Traumatology and Orthopaedics; Novosibirsk, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Mishinov
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Rogachev
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Proskurina
authors.affiliation: Mercer University School of Medicine; Macon, GA USA.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Mayorov
authors.affiliation: LLC Panagen; Gorno-Altaisk, Russia.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Shurdov
authors.affiliation: Institute of Clinical Immunology; Siberian Branch of the Russian Academy of Medical Sciences; Novosibirsk, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Ostanin
authors.affiliation: Institute of Clinical Immunology; Siberian Branch of the Russian Academy of Medical Sciences; Novosibirsk, Russia.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Chernykh
authors.affiliation: Institute of Cytology and Genetics; Siberian Branch of the Russian Academy of Sciences; Novosibirsk, Russia.
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Bogachev
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001201:Ascites / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002287:Carcinoma, Krebs 2 / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism / Q000494:pharmacology; D004705:Endocytosis; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D064593:Heterografts; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D059767:Recombinational DNA Repair / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D004247:DNA
keywords: TAMRA-labeled DNA; ascites form of Krebs-2 tumor; cyclophosphamide; human glioma neurosphere; tumor-initiating stem cells