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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.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors are grateful to Dr Mikhail P Moshkin for organizing the work at SPF animal facility, Dr Petr M Illarionov and Dr Dmitry V Subbotin for technical support, Evgeniya A Vaskova for providing the HUES9 cell line, Dr Andrey Gorchakov and Dr Robert McKallip for translation of the paper.
The work was funded by the Novosibirsk Region Long-term Target Project “Development of SMEs in Novosibirsk region in 2012-2016” (286-16/27 of 21.10.2013) and by the Novosibirsk City Budgetary Subsidy 2014 for Young Scientists and Specialists Involved in Innovative Projects (No. 15-5).