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Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development

Cancer Gene Therapy volume 20, pages 8–16 (2013)Cite this article

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Abstract

Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs in vitro, and in vivo in a preclinical model of mammary tumors induced by N-nitroso-N-methylurea (NMU). Additionally, we assessed the safety of DMSC administration in vivo and their effect on tumor growth. In vitro studies showed that DMSCs significantly migrate toward both, healthy human breast tissue and breast adenocarcinoma. Nevertheless, the effect on DMSC migration was significantly higher in the presence of tumor tissue. DMSCs also significantly migrated in vitro in the presence of NMU-mammary tumor homogenate when compared with control media alone. In vivo studies showed both migration and engraftment of DMSCs into NMU-induced tumors. Interestingly, DMSCs showed an inhibitory effect on the growth of primary tumors and in the development of new tumors. DMSCs did not affect the growth of secondary tumors, although secondary tumors appeared 2 weeks later, and the number of secondary tumors was lower in the DMSC-treated rats as compared with vehicle-treated rats. To our knowledge, this is the first report showing placental MSCs effect on tumor growth. In conclusion, DMSCs could serve as a therapeutic agent themselves and as a cellular vehicle of anticancer drugs.

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Acknowledgements

We want to thank Rafael Borsntein, MD, PhD, for his contribution to the revision and critical reading of the manuscript. This work was supported by the following grants to AI. Dr Flores: the Spanish Institute of Health Carlos III (FIS PI080137) and the MMA Foundation (FMMA 2008-108).

Author contributions

IV and AIF contributed to conception and design of the research, acquisition of data, analysis and interpretation of data, drafting and critically revision of the manuscript. MG (VMD) and MG (LA) contributed to collection of data and final approval of the manuscript. PT contributed to collection of data, data analysis and final approval of the manuscript. JG provided human material of study, and final approval of the final version of the manuscript.

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Authors and Affiliations

  1. Cancer Biology, Research Center, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain

    I Vegh

  2. Animal Core Facility, Research Center, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain

    M Grau & M Gracia

  3. Department of Obstetrics and Gynaecology, Hospital 12 de Octubre, Madrid, Spain

    J Grande

  4. Regenerative Medicine Group, Research Center, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain

    J Grande, P de la Torre & A I Flores

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  1. I Vegh
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Correspondence to A I Flores.

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Additional information

Part of this work was presented at the following conferences: The 7th Stem Cell Research and Therapeutics Conference, Boston, MA, USA, 26–27 May 2011 (Poster); CNIO Frontiers Meetings: ‘Recapturing Pluoripotency: Links Between Cellular Reprogramming and Cancer’, Madrid, Spain, 7–9 November 2011 (Poster); and The 8th Stem Cell Research and Regenerative Medicine, 19–20 April 2012 in Boston, MA (Invited Speaker).

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Vegh, I., Grau, M., Gracia, M. et al. Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development. Cancer Gene Ther 20, 8–16 (2013). https://doi.org/10.1038/cgt.2012.71

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